Powder transport systems and methods

ABSTRACT

Powder dispensing and sensing apparatus and methods are provided. The powder dispensing and sensing apparatus includes a tray support structure to receive a cartridge tray holding cartridges, a powder dispenser assembly including powder dispenser modules to dispense powder into respective cartridges of a batch of cartridges in the cartridge tray, a powder transport system to deliver powder to the powder dispenser modules, a sensor module including sensor cells to sense respective fill states, such as the weights, of each of the cartridges in the batch of cartridges, and a control system to control the powder dispenser modules in response to the respective sensed fill states of each of the cartridges of the batch of cartridges.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority based on Provisional Application Ser.No. 60/738,474, filed Nov. 21, 2005, which is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for dispensing andsensing powder and, more particularly, to methods and apparatus fordispensing precisely-controlled quantities of powder into multiplecartridges and for individually sensing the fill state of each of thecartridges. The powder can contain a drug, and the cartridges can beused in an inhaler. However, the invention is not limited to thisapplication.

BACKGROUND OF THE INVENTION

It has been proposed to deliver certain types of drugs to patients byinhalation of a powder as a delivery mechanism. One particular exampleuses diketopiperazine microparticles known as Technosphere®microparticles. The Technosphere microparticles have a platelet surfacestructure and can be loaded with a drug. See, for example, U.S. Pat. No.5,352,461, issued Oct. 4, 1994 to Feldstein et al.; U.S. Pat. No.5,503,852, issued Apr. 2, 1996 to Steiner et al.; U.S. Pat. No.6,071,497, issued Jun. 6, 2000 to Steiner et al.; U.S. Pat. No.6,428,771, issued Aug. 6, 2002 to Steiner et al.; U.S. Pat. No.6,444,226, issued Sep. 3, 2002 to Steiner et al.; and U.S. Pat. No.6,652,885, issued Nov. 25, 2003 to Steiner et al. One use of thesemicroparticles is the delivery of insulin by inhalation. An inhalerhaving a replaceable cartridge or capsule containing the drug powder isused for drug delivery.

The administration of drugs by inhalation typically requires a verysmall quantity of powder in the inhaler cartridge. By way of example,application of insulin using Technosphere microparticles can require adose of as little as 10 milligrams of the powder. In addition, the drugdose must be highly accurate. A dose lower than specified may not havethe desired therapeutic effect, while a larger than specified dose canhave an adverse effect on the patient. Furthermore, while Technospheremicroparticles are highly effective for drug delivery by inhalation,their platelet surface structure causes Technosphere powders to becohesive and somewhat difficult to handle.

In the commercialization of drug delivery by inhalation, large numbersof cartridges containing the drug must be produced in an efficient andeconomical manner. An accurate dose of powder must be delivered to eachcartridge, and the drug dose in each cartridge must be verified.Manufacturing techniques and equipment should be capable of highthroughput to meet demand and should be capable of handling powderswhich are cohesive and thus do not flow freely. Existing manufacturingtechniques and equipment have not been adequate to meet these demands.

Accordingly, there is a need for novel methods and apparatus for powderdispensing and sensing.

SUMMARY OF THE INVENTION

Systems and methods are provided for simultaneously dispensingprecisely-controlled doses of a powder into multiple cartridges. Thepowder can contain a drug, and the cartridges can be used in inhalers.The fill state of each cartridge, typically the powder weight, is sensedduring filling, and powder dispenser modules are individually controlledin response to the sensed weight to ensure accurate dosage. The systemoperates at high speed and can be very compact to enable productionfilling operations with minimal floor space requirements.

According to a first aspect of the invention, a powder dispensing andsensing apparatus comprises a tray support structure to receive acartridge tray holding cartridges, a powder dispenser assembly includingpowder dispenser modules to dispense powder into respective cartridgesof a batch of cartridges in the cartridge tray, a powder transportsystem to deliver powder to the powder dispenser modules, a sensormodule including sensor cells to sense respective fill states of each ofthe cartridges in the batch of cartridges, and a control system tocontrol the powder dispenser modules in response to the respectivesensed fill states of each of the cartridges of the batch of cartridges.

The powder dispenser modules, the powder transport system and the sensorcells can be configured for concurrent dispensing of powder to the batchof cartridges and concurrent sensing of the fill state of each of thecartridges in the batch of cartridges. The sensor cells can compriseweight sensor cells. The cartridge tray can be configured to support thecartridges in a two-dimensional array of rows and columns.

The powder transport system can include a blower assembly to move atransport gas, a powder aerator to deliver powder to the powderdispenser assembly and a hopper assembly to supply powder to the powderaerator. The powder transport system can further include a manifold thatcouples the transport gas from the powder dispenser assembly to theblower assembly to form a closed-loop recirculating gas transportsystem. The powder transport system can include a transport gasconditioning system to control the relative humidity, the temperature,or both, of the transport gas.

Each of the powder dispenser modules can include a housing that definesa powder inlet for a receiving powder from the powder transport system,a powder outlet, and a powder delivery conduit connecting the powderinlet and the powder outlet, and a feed mechanism to move powder throughthe conduit from the powder inlet to the powder outlet.

The feed mechanism can include a feed wand to move powder through theconduit, an actuator to operate the feed wand, a valve to control theoutlet, and an actuator to operate the valve. The feed wand can includea shaft and a helical open space frame including spaced-apart sparsaffixed to the shaft. The spaced-apart spars can have a helicalarrangement on the shaft. The feed wand can further comprise anarrangement of one or more wires secured between some or all of thespaced-apart spars. The wires can include one or more helix arrangementssecured between the ends of the spars and one or more chevronarrangements secured between spars at selected radial locations. In someembodiments, each wire is slidably secured through holes in intermediatespars and is attached at each end to one of the spars.

The feed wand further includes a discharge element affixed to the shaftbelow the helical open space frame. In different embodiments, thedischarge element can be implemented as a modified spar having a doublehelix configuration, a roller pin and support element used incombination with an orifice element or auger blades used in combinationwith an orifice element.

The powder dispenser assembly can include an array block having an arrayof vertical ports. The powder dispenser modules can be mounted inrespective vertical ports of the array block. The array block caninclude channels to deliver powder to the powder dispenser modules. Thepowder dispenser modules can be provided with powder inlets aligned withthe channels in the array block so that powder is delivered to a row ofpowder dispenser modules through a channel in the array block. Eachchannel in the array block can pass through the array block forrecirculating transport gas to the blower assembly. The channels in thearray block can have sufficient capacity to store powder for one or morepowder dispensing cycles of the powder dispenser modules.

The hopper assembly can include a hopper body defining a powderreservoir and a granulator in the lower portion of the powder reservoir.The granulator can comprise first and second agglomerator rollers andfirst and second motors to actuate the first and second agglomeratorrollers, respectively. Each of the agglomerator rollers can be providedwith a plurality of pins or a plurality of spaced-apart disks.

The blower assembly can include a blower to move a transport gas througha recirculating transport gas system and a gas-particle separationdevice to remove powder agglomerates from the recirculating transportgas. In some embodiments, the gas-particle separation device isimplemented as a cyclone separator and in other embodiments thegas-particle separation device is implemented as a vane separator. Theblower can include an impeller to move the transport gas, an impellermotor to rotate the impeller and a blower housing enclosing the impellerand having a discharge port to supply the transport gas to the powderaerator. The blower assembly can further comprise an induction rod tointroduce conditioned transport gas into the flow of transport gas.

The powder aerator can include a manifold block defining a powder inlet,powder output ports coupled to the powder dispenser assembly and a gasinlet coupled to the blower assembly. The powder aerator can furtherinclude a pneumatic broom to deliver powder through riser tubes to thepowder output ports and a dump valve to supply a quantity of powder fromthe powder inlet to the pneumatic broom. The dump valve also seals theclosed loop transport gas system from the external environment. Thepowder aerator can further include a bypass manifold coupled to thepowder output ports and a crossover valve that directs selected portionsof the transport gas from the gas inlet to the pneumatic broom and tothe bypass manifold.

According to a second aspect of the invention, a method is provided fordispensing and sensing powder. The method comprises positioningcartridges in a cartridge tray, concurrently dispensing powder into abatch of cartridges in the cartridge tray, and concurrently sensing afill state of each of the cartridges in the batch of cartridges.

According to a third aspect of the invention, a powder aerator comprisesa manifold block defining a powder inlet, powder output ports and atransport gas inlet; a pneumatic broom to deliver powder to the powderoutput ports; a dump valve to supply a quantity of powder from thepowder inlet to the pneumatic broom; a bypass manifold coupled to thepowder output ports; and a crossover valve to direct selected portionsof the transport gas from the gas inlet to the pneumatic broom and tothe bypass manifold.

According to a fourth aspect of the invention, a powder dispenserassembly comprises an array block including an array of vertical portsand horizontal channels intersecting each of the vertical ports; andpowder dispenser modules mounted in respective vertical ports of thearray block, each of the powder dispenser modules having powder inletscommunicating with the channels in the array block, wherein powderdelivered to the channels in the array block is dispensed by each of thepowder dispenser modules.

According to a fifth aspect of the invention, a powder transport systemcomprises a powder dispenser assembly to dispense powder intocartridges; a blower assembly to move a transport gas; and a powderaerator to deliver powder entrained in the transport gas to the powderdispenser assembly.

According to a sixth aspect of the invention, a powder dispenser modulecomprises a housing that defines a powder inlet for receiving powder, apowder outlet, and a powder delivery conduit connecting the powder inletand the powder outlet; a feed wand to move powder through the powderdelivery conduit; an actuator to operate the feed wand; a valve tocontrol the powder outlet; and an actuator to operate the valve.

According to a seventh aspect of the invention, a blower assemblycomprises an impeller to move a transport gas; an impeller motor torotate the impeller; a blower housing enclosing the impeller and havinga discharge port for the transport gas; a manifold to receive transportgas; and a gas-particle separation device affixed to the manifold toaccumulate agglomerates entrained in the transport gas.

According to an eighth aspect of the invention, a powder handlingapparatus comprises a tray support structure to receive a cartridge trayholding at least a first batch of cartridges and a second batch ofcartridges; a dispensing subsystem to dispense powder into a batch ofthe cartridges in the cartridge tray; and a tray positioning mechanismto move the cartridge tray to sequentially position the first andsubsequent batches of cartridges in the cartridge tray in alignment withthe dispensing subsystem.

According to a ninth aspect of the invention, a method for dispensingpowder into a cartridge comprises positioning a cartridge below adispenser module having a hopper containing a powder, opening a valvethat controls the hopper, operating a feed wand in the hopper todispense powder through the valve to the cartridge, and closing thevalve when a desired fill state of the cartridge is reached.

Operation of the feed wand can include rotating the feed wand andreversing rotation of the feed wand to condition the powder in thehopper. The feed wand can be rotated at variable speeds and can bedithered during rotation. The feed wand can reciprocate, causing thewand to quickly rotate clockwise and counterclockwise, during someportion of one or more revolutions. The method can include sensing aweight of powder in the cartridge and closing the valve when the sensedweight is equal to or greater than a target weight. Opening the valvecan include rotating a valve member in a selected direction, and closingthe valve can include rotating the valve member in the same direction.Opening the valve can include post-positioning the valve member withrespect to the dispenser nozzle opening.

The feed wand can be rotated at a selected maximum speed during a firstportion of a fill cycle and then rotated at a reduced speed during asecond portion of the fill cycle. The second portion of the fill cyclecan be initiated when the powder dispensed into the cartridge is equalto or greater than a selected weight. Proportional control and/orintegral control can be utilized during any portion of the fill cycle.

According to a tenth aspect of the invention, the powder dispensing andsensing apparatus is a highly compact, modular system which is operableboth in a research laboratory and in a production plant. This featurefacilitates regulatory approval for a common machine and results in costreduction due to common technical support and training and reduced partsinventories.

According to an eleventh aspect of the invention, the powder dispensingand sensing apparatus has the capability to fill inhaler cartridges, onetime use inhalers and compact multiple use inhalers. This capability canbe achieved by relatively minor changes to the system that deliverscontainers to be filled to the powder dispensing and sensing apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the present invention, reference is madeto the accompanying drawings, which are incorporated herein by referenceand in which:

FIG. 1 is a perspective view of a powder dispensing and sensingapparatus in accordance with an embodiment of the invention;

FIG. 2 is an exploded view of the powder dispensing and sensingapparatus of FIG. 1;

FIG. 3 is a partial vertical cross-sectional view of the powderdispensing and sensing apparatus;

FIG. 3A is a schematic block diagram of the powder dispensing andsensing apparatus;

FIG. 4 is a perspective view of powder dispenser modules, cartridges, acartridge tray and weight sensor cells;

FIG. 5 is a perspective view of a powder transport system;

FIG. 6 is a cross-sectional diagram of an array block and one powdertransport system;

FIG. 7 is a cross-sectional diagram of a cartridge tray and a traypositioning system;

FIG. 8 is a perspective view of an array block;

FIG. 9 is an exploded view of the array block of FIG. 8;

FIG. 10 is a perspective view of a powder dispenser module;

FIG. 11 is an exploded view of the powder dispenser module of FIG. 10;

FIG. 12 is a schematic cross-sectional diagram of the lower end of thepowder dispenser module;

FIGS. 13A-13B illustrate a feed wand in accordance with one embodimentof the invention;

FIGS. 14A-14F illustrate a feed wand in accordance with anotherembodiment of the invention;

FIGS. 15A-15D illustrate a feed wand in accordance with a furtherembodiment of the invention;

FIGS. 16A and 16B illustrate a fill valve in the open and closedpositions, respectively;

FIG. 17 is a block diagram of a control circuit for a single powderdispenser module and weight sensor cell;

FIG. 18 is a flow chart of a powder dispensing process;

FIG. 19 is a flow chart of a cartridge fill cycle;

FIG. 20 is a perspective view of the sensor module;

FIG. 21 is an exploded view of the sensor module of FIG. 20;

FIG. 22 is a perspective view of a first embodiment of a weight sensorprobe;

FIG. 23 is a perspective view of a second embodiment of a weight sensorprobe;

FIG. 24 is a perspective view of a first embodiment of a powder aerator;

FIG. 25 is an exploded view of the powder aerator of FIG. 24;

FIG. 26 is a perspective view of a pneumatic broom used in the powderaerator of FIG. 24:

FIG. 27 is an exploded view of the pneumatic broom of FIG. 26;

FIGS. 28A-28C are cross-sectional views of the powder aerator of FIG.24;

FIG. 29 is a perspective view of a second embodiment of a powderaerator;

FIG. 30 is an exploded view of the powder aerator of FIG. 29;

FIG. 31 is a perspective view of a pneumatic broom used in the powderaerator of FIG. 29;

FIG. 32 is an exploded view of the pneumatic broom of FIG. 31;

FIG. 33 is a perspective view of a first embodiment of a hopperassembly;

FIG. 34 is an exploded view of the hopper assembly of FIG. 33;

FIG. 35 is a perspective view of a second embodiment of a hopperassembly;

FIG. 36 is an exploded view of the hopper assembly of FIG. 35;

FIG. 37 is a perspective view of a first embodiment of a blowerassembly;

FIG. 38 is an exploded view of the blower assembly of FIG. 37;

FIG. 39 is a perspective view of a second embodiment of a blowerassembly;

FIG. 40 is an exploded view of the blower assembly of FIG. 39;

FIG. 41 is a schematic diagram of a gas conditioning system;

FIG. 42 is a perspective view of a powder delivery system incorporatinga sensor chamber;

FIG. 43 is an exploded view of the sensor chamber shown in FIG. 42;

FIG. 44 is a pictorial representation of a fill process for an inhalercartridge; and

FIG. 45 is a pictorial representation of a fill process for a compactinhaler.

DETAILED DESCRIPTION

Powder dispensing and sensing apparatus 10 in accordance with anembodiment of the invention is shown FIGS. 1-7. A purpose of theapparatus is to dispense powder into multiple cartridges 20 and to senseand control a fill state of each of the cartridges, so that each of thecartridges receives a precisely-controlled quantity of the powder. Asused herein, the term “cartridge” refers to any container or capsulethat is capable of holding a powder, typically a powder containing adrug substance. As used herein, the term “fill” includes filled andpartially filled, since each cartridge is typically not filled tocapacity and in fact may be filled to only a small fraction of itscapacity. As described below, the apparatus can be used to fill aninhaler cartridge or a compact inhaler, but is not necessarily limitedas to the type of container to be filled.

Cartridges 20 can be held in a cartridge tray 22 that is positioned in atray support frame 24 for processing. The cartridges can be held in anarray of rows and columns. In one example, cartridge tray 22 holdsforty-eight cartridges 20 in a 6×8 array. The configuration of cartridgetray 22 and the corresponding configuration of apparatus 10 are given byway of example only and are not limiting as to the scope of theinvention. It will be understood that cartridge tray 22 can beconfigured to hold a different number of cartridges and that cartridgetray 22 can have a different array configuration within the scope of theinvention. In another embodiment described below, the cartridge tray canhold 192 cartridges. Cartridge tray 22 can be placed in support frame 24and removed from support frame 24 by a robot.

Components of powder dispensing and sensing apparatus 10, in addition totray support frame 24, include a powder dispenser assembly 30 todispense powder into cartridges 20, a powder transport system 32 todeliver powder to powder dispenser assembly 30 and a sensor module 34 tosense a fill state of each of cartridges 20. Powder dispensing andsensing apparatus 10 further includes a frame 40 for mounting of traysupport frame 24, powder dispenser assembly 30, powder transport system32 and sensor module 34, and actuators 42 to move powder dispenserassembly 30 and powder transport system 32 with respect to cartridges20.

Powder dispenser assembly 30 includes an array block 50 having an arrayof vertical ports 52 and a powder dispenser module 54 mounted in each ofthe vertical ports of array block 50. Array block 50 can be configuredto match the array of cartridges 20 in cartridge tray 22 or a subset ofthe cartridges in the cartridge tray. In the above example of acartridge tray that holds forty-eight cartridges, array block 50 canhave a 6×8 array of vertical ports 52 and provides mounting forforty-eight powder dispenser modules 54. In this embodiment, powderdispenser modules 54 are mounted on one-inch centers. It will beunderstood that a different spacing arrangement can be utilized withinthe scope of the invention. As shown in FIG. 8, array block 50 furtherincludes powder storage and transport channels 60 a, 60 b, 60 c, 60 d,60 e, 60 f, 60 g and 60 h, with one channel for each row of six powderdispenser modules 54 in this embodiment. Powder is delivered by powdertransport system 32 to powder dispenser modules 54 through each channelin array block 50, as described below. Each channel preferably hassufficient volume to store powder for several powder dispensing cycles.

In the embodiment of FIGS. 1-7, powder transport system 32 includes afirst powder transport system 32 a to deliver powder to a first group offour channels 60 a, 60 b, 60 c and 60 d in array block 50 and a secondpowder transport system 32 b to deliver powder to a second group of fourchannels 60 e, 60 f, 60 g and 60 h in array block 50. Each of powdertransport systems 32 a and 32 b includes a blower assembly 70 to move atransport gas through the powder transport system, a powder aerator 72to deliver powder to powder dispenser assembly 30 and a hopper assembly74 to supply powder to powder aerator 72. In other embodiments, a singlepowder transport system or more than two powder transport systems can beutilized.

Blower assembly 70 is coupled through a tube 76 to a gas inlet 78 ofpowder aerator 72 and produces a flow of transport gas through gas inlet78. Powder aerator 72 includes a powder inlet 80 to receive powder fromhopper assembly 74. The powder is delivered by powder aerator 72 throughfour powder output ports 82 to inlet ends of respective channels inarray block 50. The powder is transported through the respectivechannels to the powder dispenser modules 54 in each row of powderdispenser assembly 30. The powder is individually dispensed tocartridges 20 by powder dispenser modules 54 as described below.

Channels 60 a-60 h pass through array block 50, and a tuned suctionmanifold 84 is coupled to outlet ends of the channels. The suctionmanifold 84 of first powder transport system 32 a is connected to outletends of channels 60 a-60 d, and the suction manifold 84 of second powdertransport system 32 b is connected to the outlet ends of channels 60e-60 h. Suction manifold 84 returns the transport gas to blower assembly70, thus forming a closed loop recirculating gas transport system. Inother embodiments, the powder transport system can utilize an open loopgas transport system. Any powder not delivered to powder dispensermodules 54 or stored in the channels returns through suction manifold 84to blower assembly 70. As discussed below, blower assembly 70, in someembodiments, can include a gas-particle separation device to retainlarge powder agglomerates, while small powder agglomerates arerecirculated to powder aerator 72 for delivery to powder dispenserassembly 30. As further discussed below, each powder transport systemcan include a gas conditioning unit to control the relative humidityand/or temperature of the recirculating transport gas.

The powder transport system 32 can include sensors to determine thepowder level in different components of the powder transport system.Hopper assembly 74 can include a hopper level sensor to sense the powderlevel in the reservoir of hopper assembly 74. Powder aerator 72 caninclude a dump valve level sensor to determine the powder level in thedump valve of powder aerator 72. The blower assembly 70 can include alarge agglomerate level sensor. A dispenser fill level sensor can belocated at the suction manifold 84 of blower assembly 70. The powderlevel sensors can use optical techniques to sense powder level, forexample. The powder level sensors can be used to control operation ofpowder delivery system 32 and loading of powder dispenser modules 54with powder.

Sensor module 34 (FIG. 20) can include a sensor housing 100 (FIG. 21)and an array of sensor assemblies 110 mounted in sensor housing 100. Inthe illustrated embodiment, each of the sensor assemblies 110 includestwo sensor cells 114 (FIG. 3) and associated circuitry. Thus, one sensorassembly 110 is used with two powder dispenser modules 54. In otherembodiments, each sensor assembly can include a single sensor cell ormore than two sensor cells. The number of sensor assemblies 110 and thearrangement of sensor assemblies 110 in the array can be such that thesensor cells 114 match the configuration of cartridges 20 in cartridgetray 22 or a subset of the cartridges in the cartridge tray. For theexample of a cartridge tray 22 that holds forty-eight cartridges 20 in a6×8 array on one inch centers, the sensor module 34 can includetwenty-four sensor assemblies 110, which provide forty-eight sensorcells 114 in a 6×8 array on one inch centers. In the embodiment of FIGS.1-7, each of the sensor cells 114 is a weight sensor to sense the weightof the powder delivered to the respective cartridge 20. A weight sensorprobe 112 is affixed to each of the sensor cells 114 and contacts alower end of cartridge 20 through an opening in cartridge tray 22.

The sensor cells 114 individually sense the fill state of each ofcartridges 20 during dispensing of powder, so that powder dispensing canbe terminated when the desired amount of powder has been dispensed intoeach cartridge 20. The sensor cells 114 are preferably weight sensorswhich monitor the weight of cartridge 20 during the powder dispensingprocess and are accurate within 5 to 10 micrograms in the presentembodiment. An electrobalance beam is typically used as a weight sensorin applications requiring high accuracy, high speed and repeatabilitywith very small weights.

The physical configuration of the weight sensor assembly 110 is aconsideration in systems where powder dispenser modules 54 are closelyspaced, such as on one inch centers. Preferably, the weight sensorassemblies 110 can be placed in an array that matches the configurationof cartridge tray 22 and powder dispenser modules 54. In a preferredembodiment, sensor assemblies 110 have a vertical configuration and twosensor cells 114 are packaged together to form a sensor assembly. Theweight sensing mechanical components are located at the top of theassembly, electrical circuitry is located below the mechanicalcomponents and an electrical connector is located at the bottom. Thesensor assemblies can be mounted in an array for weight sensing on oneinch centers.

In another embodiment, a commercially available weight sensor module hasa horizontal configuration and can be utilized in a tiered arrangementon three different levels for an array having six cartridges per row. Inthe tiered arrangement, probes of different lengths are used to contactthe cartridges.

The powder dispensing and sensing apparatus 10 has been described ashaving powder dispenser modules 54 and sensor cells 114 mounted on oneinch centers. It will be understood that a larger or smaller spacingbetween components can be utilized within the scope of the invention.Further, the components of the apparatus 10 are not necessarily mountedin a uniform array. For example, the x-direction spacing betweencomponents can be different from the y-direction spacing betweencomponents, or a row of the array can be offset with respect to anadjacent row.

In operation, cartridge tray 22 holding cartridges 20 is positioned intray support frame 24, preferably by a robot or other automationmechanism. Cartridge tray 22 is lowered so that cartridges 20 are raisedfrom cartridge tray 22 by weight sensor probes 112 on respective sensorassemblies 110 and are supported by probes 112. Cartridge tray 22 can beprovided with openings at each cartridge location to permit probes 112to pass through cartridge tray 22 and lift cartridges 20. Thus, eachcartridge 20 can be weighed by one of the sensor cells 114 withoutinterference from cartridge tray 22. In some embodiments (FIGS. 22 and23), probe 112 includes a three-point support for cartridge 20. In otherembodiments, probe 112 includes a cylindrical support for cartridge 20.Powder dispenser assembly 30 is lowered to a dispensing position. In thedispensing position, each powder dispenser module 54 is positionedslightly above and in alignment with one of the cartridges 20.

As shown in FIG. 2, frame 40 can include a lower frame 40 a, a middleframe 40 b and an upper frame 40 c. Lower frame 40 a and middle frame 40b are secured to a base plate 41. Upper frame 40 c provides mounting fortray support frame 24, powder dispenser assembly 30 and powder transportsystem 32. Array block 50 is connected to actuators 42 and movesupwardly or downwardly when actuators 42 are energized. Sensor module 34is mounted in a fixed position within lower frame 40 a and middle frame40 b.

As discussed below, powder transport system 32 can operate continuouslyor at intervals. The powder dispenser modules 54 are activated todispense powder to cartridges 20. The dispensing of powder to cartridges20 is performed concurrently, so that all cartridges in cartridge tray22 or a subset of the cartridges in the cartridge tray receive powdersimultaneously. As powder dispensing progresses, the weights ofcartridges 20 are sensed by respective sensor cells 114. The output ofeach sensor cell 114 is coupled to a controller. As discussed below,each controller compares the sensed weight with a target weight whichcorresponds to the desired quantity of powder. As long as the sensedweight is less than the target weight, powder dispensing continues. Whenthe sensed weight is equal to or greater than the target weight, thecontroller commands the corresponding powder dispenser module 54 toterminate the powder dispensing operation. If the sensed weight exceedsa maximum allowable weight after the fill cycle, the correspondingcartridge can be marked as defective. Thus, powder dispensing and weightsensing proceed concurrently for a batch of cartridges in cartridge tray22. The batch can include all the cartridges in cartridge tray 22 or asubset of the cartridges in the cartridge tray. A powder dispensingcycle can include concurrent dispensing of powder to and weight sensingof a batch of cartridges and achieves 100% inspection and control ofpowder dispensing.

In one embodiment, the number and spacing of cartridges in cartridgetray 22 matches the number and spacing of powder dispenser modules 54 inapparatus 10. In other embodiments, the cartridge tray can have adifferent number of cartridges and a spacing between cartridges that isdifferent from the configuration of powder dispenser modules 54. Forexample, the cartridge tray can be configured to hold a multiple of thenumber of powder dispenser modules 54 and to have a smaller spacingbetween cartridges than the spacing between powder dispenser modules 54.By way of example only, the cartridge tray can be configured to hold 192cartridges 20 spaced on one-half inch centers. With this arrangement, a12×16 array of cartridges on one-half inch centers occupies the samearea as a 6×8 array of cartridges on one inch centers.

As shown in FIG. 7, the cartridge tray 22 can be displaced in ahorizontal direction by a tray positioning mechanism 120 to aligndifferent batches of cartridges with powder dispenser modules 54.Cartridge tray 22 is positioned in tray support frame 24 for processing.Tray positioning mechanism 120 includes an X-direction actuator 230coupled to tray support frame 24 and a Y-direction actuator 232 coupledto tray support frame 24. Thus, tray support frame 24 and cartridge tray22 can be moved in a horizontal X-Y plane for positioning of batches ofcartridges in relation to powder dispenser modules 54 and sensor cells114.

The cartridge tray with 192 cartridges can be processed as follows. Thecartridge tray is moved from a neutral position to a first X-Y position(0,0) such that a first batch of 48 cartridges is vertically alignedwith the array of 48 powder dispenser modules 54. Powder is dispensedinto the first batch of cartridges and then the cartridge tray is movedto a second X-Y position (0, 0.5) to align a second batch of 48cartridges with the array of 48 powder dispenser modules 54. Powder isdispensed into the second batch of cartridges and then the cartridgetray is moved to a third X-Y position (0.5, 0) to align a third batch of48 cartridges with the array of 48 powder dispenser modules 54. Thecartridge tray is then moved to a fourth X-Y position (0.5, 0.5) toalign a fourth batch of 48 cartridges with the array of 48 powderdispenser modules 54. Powder is dispensed into the fourth batch ofcartridges to complete processing of the 192 cartridges. In the aboveexample, the order of the tray positions and the order of the batches ofcartridges can be changed.

It will be understood that this process can be applied to different trayarrangements with a different spacing between cartridges, differentnumbers of cartridges, and the like. In these embodiments, the cartridgetray is displaced in the horizontal plane to achieve alignment betweenbatches of cartridges and the array of powder dispenser modules. Thebatch of cartridges typically matches the array of powder dispensermodules 54. However, in some applications the batch can have fewercartridges than the number of powder dispenser modules.

Array block 50 is shown in FIGS. 8 and 9. As described above, arrayblock 50 is provided with powder storage and transport channels 60 a, 60b, 60 c, 60 d, 60 e, 60 f, 60 g and 60 h, one channel corresponding toeach row in the array of powder dispenser modules 54. Each of thechannels 60 a-60 h extends through array block 50 and intersects thevertical ports 52 in the corresponding row of the array. In theembodiment of FIGS. 1-7, powder transport system 32 a delivers powder toone side of array block 50, and powder transport system 32 b deliverspowder to the opposite side of array block 50. Accordingly, FIGS. 8 and9 show the inlet ends of channels 60 a-60 d and the outlet ends ofchannels 60 e-60 h.

In the embodiment of FIGS. 8 and 9, channels 60 a-60 h have slot-shapedcross-sections and are parallel. As shown in FIG. 10, each of the powderdispenser modules 54 is provided with a powder inlet 130 in the form ofa slot-shaped opening that passes through the powder dispenser module.When powder dispenser modules 54 are mounted in array block 50, powderinlets 130 are aligned with the corresponding channel in array block 50.Powder inlets 130 and channels 60 a-60 h preferably have cross sectionsof equal sizes and shapes and are polished to provide smooth insidesurfaces. Each channel in array block 50 and the corresponding powderinlets 130 in powder dispenser modules 54 define a passage through arrayblock 50 for delivery of powder to each of the powder dispenser modules54. Powder is supplied to each of powder dispenser modules 54 throughpowder inlet 130. Powder inlet 130 is configured as a through opening sothat part of the powder transported through the channel is delivered tothe first powder dispenser module 54 and another part of the powder istransported through powder inlet 130 and the channel in array block 50to successive powder dispenser modules 54.

In addition, channels 60 a-60 h serve a powder storage function.Channels 60 a-60 h can store more powder than is needed for dispensingto a single batch of cartridges. In one embodiment, powder transportsystem 32 operates at intervals. Sufficient powder for a number ofbatches of cartridges 20 is supplied from hopper assembly 74 to channels60 a-60 h. Then, powder is dispensed to several batches of cartridges 20until the powder supply in dispenser modules 54 becomes low. In otherembodiments, powder is supplied continuously to channels 60 a-60 h, andchannels 60 a-60 h serve as buffers to store powder not dispensed tocartridges 20.

The closed-loop pneumatic powder transport system 32 feeds theagglomerate particles into the array block 50 from the powder aerator72. Then, the transport gas is recirculated back to powder aerator 72.The transport gas can be conditioned by a secondary process control gasthat is supplied to the blower assembly 70.

The array block 50 functions as a dynamic powder storage device thatfeeds batch loads or continuous loads of drug powder into individualpowder dispenser modules 54. More generally, the array block 50 includesone or more channels used to transport powder aerosols and/oragglomerate slurries of drug powders to an array of powder dispensermodules. The array block 50 can operate in an open loop or a closed loopgas transport system. The powder aerator 72 and the array block 50fluidize, entrain and transport drug powder into the channels of arrayblock 50.

Array block 50 can provide the main structural support for associatedcomponents and subsystems, such as powder aerator 72, hopper assembly74, suction manifold 84, and pump assembly 70. In addition, array block50 holds an array of powder dispenser modules 54 for dispensing powderto an array of cartridges. In a preferred embodiment, the array blockincludes a main block 132, a top plate 134 and a bottom plate 136.Plates 134 and 136 include O-rings which serve as guides and seals forpowder dispenser modules 54. This array block further includes bearings140 and clamping handles 142 for attachment of the array block to framemembers.

In operation, powder is transported through each of channels 60 a-60 hby the transport gas and is delivered to each of the powder dispensermodules 54 in a controlled particle deposition process. The powder dropsby action of gravity into each of the powder dispenser modules 54. Anypowder that passes through the channel without dropping into one of thepowder dispenser modules 54 and without being stored returns throughsuction manifold 84 to pump assembly 70.

Each powder dispenser module 54 dispenses powder into a cartridge 20.The powder dose is typically in a range of 5 to 30 milligrams, but thedose is not limited to this range.

As shown in detail in FIGS. 10-16B, powder dispenser module 54 includesa powder dispenser housing 150 having a lower housing section 150 a, amiddle housing section 150 b, an upper housing section 150 c and a cover150 d. The powder dispenser housing 150 can have an elongatedconfiguration with a small cross section to permit close spacing inarray block 50. As noted above, powder dispenser modules 54 can bemounted on one inch centers. Middle housing section 150 b includespowder inlet 130 and a cylindrical conduit 152 that extends downwardlyfrom powder inlet 130 to lower housing section 150 a. Lower housingsection 150 a includes a tapered conduit 154 that extends downwardly toa dispenser nozzle 158, which is dimensioned for compatibility withcartridge 20. The tapered conduit 154, which can be conical in shape,provides a transition from the dimension of cylindrical conduit 152 tothe dimension of dispenser nozzle 158. Together, cylindrical conduit 152and tapered conduit 154 define a dispenser hopper 156 for holding powderto be dispensed. The powder in dispenser hopper 156 is termed a bulkpowder bed. Dispenser nozzle 158 is configured to dispense powder intocartridge 20.

Powder dispenser module 54 further includes a feed wand 160 to movepowder downwardly in a controlled manner through dispenser hopper 156 tonozzle 158, a wand actuator 162 to actuate wand 160, a dispenser fillvalve 180 at the lower end of hopper 156, and a valve actuator 182 toopen and close valve 180. Wand actuator 162 and valve actuator 182 canbe miniature motors. Wand actuator 162 can be coupled to feed wand 160by a flexible coupling 186 or other coupling which can provide verticalwand agitation, displacement, or both, in addition to rotation. Powderdispenser module 54 further includes a circuit board 184 havingcircuitry for controlling wand actuator 162 and valve actuator 182 andfor communicating with control circuitry that controls operation ofpowder dispenser module 54.

Fill valve 180 can include a valve member 190 implemented as a gearprovided with an eccentrically-located valve opening 191. Valve member190 can be mounted in lower housing section 150 a for rotation about anaxis such that valve opening 191 can be rotated into alignment withdispenser nozzle 158, as shown in FIG. 16A, and can be rotated out ofalignment with dispenser nozzle 158 as shown in FIG. 16B. When valveopening 191 and dispenser nozzle 158 are aligned or partially aligned,fill valve 180 is open and powder is dispensed into a cartridge. Whenvalve opening 191 is not aligned with dispenser nozzle 158, fill valve180 is closed and powder is not dispensed. Preferably, fill valve 180 isa type that can be partially opened, as described below.

Valve member 190 of fill valve 180 can be coupled to valve actuator 182by a drive assembly including a lower gear 192 that meshes with the gearof valve member 190, a drive shaft 193 that extends from a lower portionof dispenser module 54 to an upper portion thereof where valve actuator182 is mounted, an upper gear 194 attached to the upper end of driveshaft 193 and an upper a gear 195 attached to valve actuator 182. Uppergears 194 and 195 are interengaged such that valve member 190 is causedto rotate when valve actuator 182 is energized.

Gear 195 can match valve member 190, and gear 194 can match gear 192.Thus, the position of gear 195 is indicative of the position of valvemember 190 and the position of valve opening 191 relative to nozzle 158.A magnet attached to upper gear 195 rotates relative to open and closedsensors 220 (FIG. 17) to indicate the open and closed positions,respectively, of fill valve 180.

A schematic cross-sectional diagram of the lower end of powder dispensermodule 54, between powder inlet 130 and dispenser nozzle 158, is shownin FIG. 12. As shown, dispenser hopper 156 may be considered as having apowder bed preparation zone 156 a, a powder bed compression zone 156 band a discharge zone 156 c. Powder bed preparation zone 156 a is locatedin the cylindrical conduit 152 below powder inlet 130. Powder bedcompression zone 156 b is located in an upper portion of tapered conduit154, and discharge zone 156 c is located in a lower portion of taperedconduit 154.

Feed wand 160 can include a shaft 170 in the form of a rod that extendsaxially through dispenser hopper 156. Feed wand 160 further includes oneor more feed elements affixed to shaft 170. The feed elements movepowder from powder inlet 130 to dispenser nozzle 158 in a controlledmanner. In the embodiment of FIG. 12, feed wand 160 includes a powderbed preparation element 164 in powder bed preparation zone 156 a, apowder bed compression element 165 in powder bed compression zone 156 band a discharge element 166 in discharge zone 156 c. Examples of feedelements 164, 165 and 166 are described below.

One embodiment of feed wand 160 is shown in FIGS. 13A and 13B. In thefeed wand embodiments described herein, the powder bed preparationelement 164 and the powder bed compression element 165 are implementedas a helical open space frame, including a plurality of spaced-apartspars 172 mounted to shaft 170 and one or more wires affixed to spars172 and shaft 170. Spars 172 can extend radially from shaft 170 incylindrical conduit 152 and tapered conduit 154. Spars 172 can extendnearly to the inside wall of hopper 156 without contacting the insidewall. The spars 172 in tapered conduit 154 vary in length to match theconical inside wall of tapered conduit 154. Spars 172 are mounted toshaft 170 in different radial directions. In a preferred embodiment, theends of spars 172 define a double helix.

In the embodiment of FIGS. 13A and 13B, feed wand 160 includes tenspars. In this example, adjacent spars are spaced apart along shaft 170at 0.125 inch intervals, and each spar is rotated by 45 degrees relativeto the adjacent spar, except for the last two spars at the bottom ofshaft 170, which are rotated by 22.5 degrees. The spar diameter can bethe preferred agglomerate size, on the order of 0.025 to 0.075 inch. Thespar material can be stainless steel or other structurally stiff, inertmaterial that is corrosion-resistant, such as metal, ceramic, plasticand the like. The feed wand can be made of conductive or non-conductivematerial, depending on the powder morphology. Non-conductive materialssuch as ceramics, plastics and elastomers can be metallized to provide aconductive outer surface. Too many spars cause the powder to compactwith wand rotation, whereas too few spars will not support the doublehelix configuration. The spacing between spars and the angle betweenadjacent spars can be inversely proportional to the number of sparsused.

As noted above, feed wand 160 includes wires affixed to spars 172. Inthe embodiment of FIGS. 13A and 13B, the wires define a double helix174, a first chevron 176 and a second chevron 178. As shown, doublehelix 174 includes a helix wire 174 a at or near one end of each spar172 and a helix wire 174 b at or near the opposite end of each spar 172.Each helix wire 174 a, 174 b progresses downwardly from spar to spar ina clockwise direction as viewed downwardly from wand actuator 162.

First chevron 176 can include a first chevron wire 176 a affixed tospars 172 at a first spacing from shaft 170, and second chevron 178 caninclude a second chevron wire 178 a affixed to spars 172 at a secondspacing from shaft 170. First chevron wire 176 a passes through a hole176 b in shaft 170, and second chevron wire 178 a passes through a hole178 b in shaft 170. It will be understood that the helix wires and thechevron wires are not necessarily affixed to every spar in the feed wand160. In particular, first chevron wire 176 a is affixed to the firstspar (the uppermost spar) and the fifth spar. Second chevron wire 178 ais affixed to the third spar and the seventh spar. The first and secondchevrons can be spaced by 90° relative to each other.

In the embodiment of FIGS. 13A and 13B, the helix wires and the chevronwires are threaded through holes in the respective spars and areattached at each end. The helix wires are located at or near the ends ofthe spars, and the chevron wires are located at desired spacings fromshaft 170. The holes in spars 172 can be tool drilled, laser drilled oredm drilled. In a preferred embodiment, the holes in spars 172 are edmdrilled at angles that avoid significant bending of the wires. Thus, theholes in each spar are approximately aligned with the adjacent spars.This arrangement permits the wires to slide through the holes more orless freely so that the powder loading forces are distributed along theentire wire length, thereby reducing the wire stress concentration whichcould cause breakage. In other embodiments, the wires can be attached tothe spars, such as by laser welding for example. In this example, thehelix wires and chevron wires are 0.008 inch in diameter.

The double helix 174 can be formed by lacing the outer ends of thehelically-mounted spars 172 with helix wires 174 a and 174 b. Wiring thespars 172 on both outer ends creates a double helix wire pattern. Thedouble helix wire pattern performs three main functions. First, theperimeter wire inhibits compressed powders from adhering to conduitwalls, particularly the walls of tapered conduit 154. Second, when thewand 160 is rotated clockwise (from the actuator shaft lookingdownward), the double helix lifts the powder at the conduit wallinterface and further reduces it into the preferred agglomerateflowability size range. Third, when the wand 160 is rotatedcounterclockwise, the double helix feeds the bulk powder down along theshaft 170, as well as along the chevron wire free paths and into thedispenser nozzle 158. In addition, this rotary bulk powder feedoperation tends to break up compressed powder disks which formhorizontally between the rotating spars 172.

The feed wand 160 utilizes a helical open space frame that includesshaft 170 as a center support, spars 172 as structural cross memberswhich form a helical pattern with a conically tapered lower endgeometry, and wires that form double helix 174 and first and secondchevrons 176 and 178, as described above. The inverted conical shapetransitions the spars from a larger diameter conduit to a smallerdiameter powder discharge nozzle. Wires are affixed to the spars toreduce bulk powder compression effects and to promote flow of theagglomerate slurry. The feed wand 160 has the capability of transportinghighly cohesive powders with microgram dispensing precision, whilecontrolling the tendency for bulk powder compaction. Powder compactionleads to powder compression lock-up and thus causes dispenser clogging.The helical open space frame provides an optimal bulk powder transportmember which is capable of precision transport and dispensing of alltypes of powder morphologies from free flowing to highly cohesive. Thiscapability is achieved by allowing only a minor portion of the helicalmechanical forces to be directed downwardly into the bulk powder bed,thus controlling compression effects appropriately to the individualcharacteristics of the powder being dispensed. Because of thiscompression control, it is possible to transport cohesive powders from alarge diameter conduit to a smaller one in an effective manner.

Shaft 170 forms the central drive shaft of the feed wand 160. Shaft 170supports spars 172, double helix 174 and first and second chevrons 176and 178 which, in turn, transport bulk powder for precision dispensing.The central drive shaft allows fine powders to flow along its smoothsurface toward dispenser nozzle 158.

Spars 172 are structural cross-members that break up the compactedpowder agglomerate bed. Spars 172 also support the helix and chevronwires. In addition, spars 172 provide the helical spiral mechanismnecessary to convey the bulk powder bed in a controlled, low compressionmanner.

The chevron wires 176 a and 178 a provide cutting patterns within thebulk powder bed. The wires are located to reduce the compacted powderand to open a temporary free path within the powder bed that allowsminute amounts of powder agglomerates to flow downwardly through thepowder bed by gravity. In addition, the chevron wires sever the bulkpowder disk that forms between spars 172. These disks are created byprogressive compaction forces and form suspended aggregate powderstructures. By cutting the disks, preferably at mid-span, the disksbecome structurally unstable and begin to break up and flow downwardly,driven by the mechanical forces from the helically-pitched spars 172.

The discharge element 166 (FIG. 12) is contoured and located to break upa powder compression disk located at the dispenser nozzle 158. Thepowder disk forms when the feed valve 180 is closed and the wand 160 isperforming bulk powder raking and grooming operations. Without thedischarge element 166 to dislodge and reduce the disk, the disk wouldeither clog the nozzle or would fall into the cartridge when the valveopens, possibly causing cartridge overfill. The powder disk has thegreatest tendency to block the nozzle when the ambient humidity is above50 percent.

Embodiments of discharge element 166 are shown in FIGS. 13A-13B, 14A-14Fand 15A-15D. Each of the embodiments uses the helical open space frameof spars and wires described above, but uses different dischargeelements. Powder is induced to fall in powder bed preparation zone 156 aby rotating the helical open space frame described above. The outerhelical wires break attraction forces between the powder and thecylindrical conduit wall, and lift and aerate the powder bed whenrotated in the reverse direction. The chevron wires cut and furtherreduce the powder bed as the helical space frame rotates. The powder bedpreparation zone 156 a enhances the flowability of the powder bed as itenters the tapered conduit of powder bed compression zone 156 b. Thepowder flowability is enhanced by the ability of the helical open spaceframe to form natural agglomerates that allow the powder to flow wheninduced by the forces of the helical open space frame. In the powder bedcompression zone 156 b, the agglomerated powder bed experiencescompression due to the volume reduction of the tapered conduit. Thecompression zone steadily increases the consolidation of the powder bed,while the spars and wires continue to reduce and aerate the powder bed.In discharge zone 156 c, the powder agglomerate clumps are furtherreduced and discharged through nozzle 158. The discharge elementcontrols the reduction and dispensing characteristics of the powder.Inadequate powder reduction control causes the discharge orifice toclog. Inadequate powder reduction control also inhibits powderdispensing within a specified time limit without dose overshoot. Thedischarge element determines the final powder dispensing flow rate andpowder agglomerate consistency.

In the embodiment of FIGS. 13A-13B, the discharge element 166 isconfigured as a modified spar 181. The two sides 181 a and 181 b ofmodified spar 181 extend downwardly in a one-half turn counterclockwisehelix, thus forming a double helix. Double helix modified spar 181 anddouble helix 174 have opposite pitches. In other embodiments, one sideof the modified spar is turned upwardly in a helical shape. The modifiedspar can use a clockwise or counterclockwise helix. In some embodiments,the modified spar can be formed as an inverted U-shape or as an S-shape.The U-shape works better for free-flowing powders, while the S-shapeperforms better for cohesive powders. In the U-shape, both sides of themodified spar are turned toward the dispenser nozzle. In the S-shape,one side of the modified spar is turned toward the dispenser nozzle andthe other side is turned upwardly.

The double helix modified spar 181 of FIGS. 13A-13B functions as arotating polarizing element within the lower end of the tapered conduit.The reverse pitch geometry of the modified spar adds powder lift andaeration to control powder dispensing and to enhance powder consistency.The reverse pitch geometry also drives powder toward the nozzle duringthe raking cycle. This creates an initial 2 to 4 milligram powder dumpat the beginning of the dispensing cycle and allows more time forfilling at the end.

Another embodiment of feed wand 160 is shown in FIGS. 14A-14F. In theembodiment of FIGS. 14A-14F, the discharge element 166 is implemented asa roller pin 183 mounted to shaft 170 by a support element 185 having aninverted U-shape. In the embodiment of FIGS. 14A-14F, an optionalmulti-slot baffle disk 189 can be located in the upper portion oftapered conduit 154 and affixed to lower housing section 150 a.

Powder dispenser module 54 further includes an orifice element 187mounted in the lower end of tapered conduit 154. Orifice element 187 mayhave one or more slot-shaped orifices. In one embodiment shown in FIG.14D, an orifice element 187 a includes two slot-shaped orifices thatintersect to form a cross. In other embodiments, orifice elements 187 band 187 c include three intersecting slot-shaped orifices, as shown inFIGS. 14E and 14F. The orifices may be relatively wide, as shown in FIG.14E, or relatively narrow, as shown in FIG. 14F. Feed wand 160 ispositioned such that roller pin 183 is spaced from orifice element 187by a spacing of less than the natural agglomerate size. In operation,roller pin 183 rotates relative to orifice element 187, causing powderto be discharged through the orifices in orifice element 187.

The baffle disk 189 can be used to control the powder bed advancementrate and to further reduce powder agglomerates as they enter the taperedconduit. In the discharge zone 156 c, powder agglomerate clumps arereduced and then extruded by the rotating roller pin 183 through theorifices in orifice element 187. The mechanism including support element185, roller pin 183 and orifice element 187 control the reduction anddispensing characteristics of the powder. Inadequate powder reductioncontrol causes the discharge orifice to clog. Inadequate powderreduction control also inhibits powder dispensing within a specifiedtime limit without dose overshoot. The support element 185 and theroller pin 183 determine the final powder dispensing flow rate andpowder agglomerate consistency. The mechanism including support element185, roller pin 183- and orifice element 187 can be configured toprovide an optimum powder flow and agglomerate size for a particularpowder morphology. The support element 185 tracks in a perimeter grooveof lower housing section 150 a to self-center the feed wand 160. Theroller pin 183 combined with orifice element 187 produces low forcepowder agglomerate dispensing. The orifice element 187 provides powderagglomerate consistency within a tighter agglomerate size range.

A further embodiment of feed wand 160 is illustrated in FIGS. 15A-15D.Discharge element 166 is implemented as helical auger blades 240 and 242affixed to shaft 170. Each auger blade 240, 242 has approximatelyone-half turn around shaft 170. The axial length of auger blades 240 and242 can be approximately one-half of the axial length of tapered conduit154. As shown, the feed wand of FIGS. 15A-15D uses fewer spars than theembodiment of FIGS. 13A-13B, and the helix wires and chevron wires canbe affixed to the upper edges of auger blades 240 and 242. Auger blades240, 242 and double helix 174 can have opposite pitches.

The powder dispenser module 54 shown in FIGS. 15A-15D further includesan orifice element 244 mounted in the lower end of tapered conduit 154.In the embodiment of FIGS. 15A-15D, orifice element 244 has an invertedconical shape and is provided with a plurality of orifices 244 a fordischarge of powder through nozzle 158. Further, the lower edges ofauger blades 240 and 242 are angled to match inverted conical orificeelement 244. A bearing 246 mounted at the lower end of shaft 170 engagesan opening in orifice element 244 and establishes a desired spacingbetween auger blades 240, 242 and orifice element 244. The bearing 246can be a jewel material, such as ruby or sapphire, which isnon-contaminating to the dispensed drug powder. In operation, augerblades 240 and 242 rotate relative to orifice element 244, causingpowder to be discharged through the orifices in orifice element 244. Inother embodiments, the orifice element can be flat, as shown in FIGS.14D-14F, and the lower edges of auger blades 240 and 242 are flat tomatch the orifice element.

This embodiment rotates opposite to the feed wands shown in FIGS.13A-13B and 14A-14F. In the discharge zone 156 c, powder agglomeratesare caused to flow by the reverse pitch auger blades and then extrudedand granulated by the rotating auger tip through the orifices in orificeelement 244. The mechanism of auger blades and orifice element controlsthe reduction and dispensing characteristics of the powder. Inadequatepowder reduction control causes the discharge orifice to clog.Inadequate powder reduction control also inhibits dispensing within aspecified time limit without dose overshoot. The mechanism of augerblades 240, 242 and orifice element 244 has the capability ofcompensating for the variability of the powder bed fluidic head height,thus reducing the sensitivity of the dispensing process to the powderbed head conditions. The half-turn double helix of the auger bladesisolates vertical fluidic bed forces from the powder in the nozzle, thuseliminating the force vectors which tend to pack powder in the nozzle.The mechanism of auger blades 240, 242 and orifice element 244 can beconfigured to provide optimum monotonic powder agglomerate sizes. Themechanism provides powder agglomerate consistency within a tighteragglomerate size range. The bearing 246 provides auger alignment andsupport, while maintaining auger-to-orifice powder membrane thickness.

In some embodiments, the discharge element 166 is mounted in a hole inthe tip of shaft 170. In other embodiments, the discharge element 166 isimplemented on a removable tip of shaft 170. For example, a double helixdischarge element can be formed on a removable tip that is press fitinto the end of shaft 170. The removable tip can be changed toaccommodate different powder morphologies.

The following discussion of the operation of powder dispenser module 54refers to raking operations and dispensing operations for theembodiments of FIGS. 13A-13B and 14A-14F. Raking is an operation togroom and recondition a powder bed into an evenly aerated, preferredagglomerate size matrix, thus providing greater flowabilitycharacteristics for bulk powder transport. The preferred agglomeratesize is the natural, stable size of cohesive powder agglomerates createdby a powder bed tumbling operation and is typically in a range of 0.025inch to 0.075 inch spherical diameter. Powder bed raking can beperformed in the down-feed or uplift modes. However, cohesive powdersprefer uplift raking to achieve optimal aeration and enhancedflowability. Dispensing is an operation to transport dry bulk powder ina “sprinkling” manner, falling under the force of gravity withoutcompression, as a preferred agglomerate matrix, discharged from a powdernozzle that dispenses into a cartridge. The powder dispensing andsensing apparatus described herein is capable of operation with powderagglomerates in a range of 0.005 inch to 0.075 inch spherical diameter,but is not limited to this range.

The feed wand 160 is rotated in a clockwise direction as viewed from thetop of the dispenser module 54 to rake, groom and aerate the bulk powderbed. Clockwise rotation lifts the powder due to an upward flow vectorcreated by the double helix. In this operation, the wand can be viewedas a screw, held vertically at its cap, being rotated into the powder.The double helix scrapes the conduit walls and also moves the outeragglomerates toward the center of the dispenser hopper. As the wandrotates, the spars force large agglomerates to break up evenly. Thisaerates the bulk powder bed, creating better bed consistency.

To dispense the powder, the wand 160 is preferably rotated in acounterclockwise direction. Spars 172 and chevrons 176, 178 break up thepowder bed and open a free path for the powder to flow along shaft 170.The double helix 174 adds a downward compression vector to drive thepowder down and through the dispenser nozzle 158. In other embodiments,the wand 160 is rotated in a clockwise direction to dispense powder.However, the agglomerates tend to be larger and the tendency to overfillis much greater for powder dispensing by rotation in the clockwisedirection.

In the embodiments described above, the spars and the helix wires have aclockwise configuration as viewed from the top. It will be understoodthat the arrangement of the spars and wires of the feed wand can bereversed within the scope of the invention. Thus, the spars and thehelix wires can have a counterclockwise configuration as viewed from thetop. In this configuration, the wand is preferably rotated in aclockwise direction to dispense powder.

The following discussion of the operation of powder dispenser module 54refers to raking operations and dispensing operations for theembodiments of FIGS. 15A-15D. The feed wand 160 is rotated in acounterclockwise direction as viewed from the top of the dispensermodule 54 to groom the bulk powder bed and fill the auger. The doublehelix 174 adds a downward compression vector to drive the powder downand into the dispenser nozzle 158. At the same time, the auger blades240, 242 supply upward force vectors on the powder to bring the powderin the auger up into the upper bed for aeration.

To dispense the powder, the feed wand 160 is preferably rotated in aclockwise direction. Clockwise rotation lifts the upper bed powder dueto an upward flow vector created by the double helix of the helical openspace frame. In this operation, the upper wand can be viewed as a screw,held vertically at its cap, being rotated into the powder. The doublehelix scrapes the conduit walls and also moves the outer agglomeratestoward the center of the dispenser hopper. As the wand rotates, thespars force large agglomerates to break up evenly. This aerates the bulkpowder bed, creating better bed consistency. Spars 172 and chevrons 176,178 break up the powder bed and open a free path for the powder to flowalong shaft 170.

The powder in the auger when dispensing first starts is forced throughthe nozzle by the downward force vectors of the auger. Duringdispensing, additional powder is supplied by the aerated powder fallingfrom the upper bed.

In the embodiment described above, the spars and the helix wires have aclockwise configuration as viewed from the top. It will be understoodthat the arrangement of the spars and wires of the feed wand can bereversed within the scope of the invention. Thus, the spars and thehelix wires can have a counterclockwise configuration as viewed from thetop. In this configuration, the wand is preferably rotated in acounterclockwise direction to dispense powder.

A block diagram of a controller for a single powder dispenser module 54and the corresponding sensor cell 114 is shown in FIG. 17. Preferably,the powder dispenser controls provide strategically concentratedredundant computing power at the lowest level. Powder dispenser module54 includes a dispenser controller 200 (FIG. 17) on circuit board 184(FIG. 11). Dispenser controller 200 can include three processors. Oneprocessor is provided for each of wand actuator 162 and valve actuator182, and one processor is used to control status LEDs 224 and optionalanalog sensor inputs. A control processor 210 is located on a backplaneof sensor module 34 as described below. The system utilizes one controlprocessor 210 for each dispenser module 54 and its associated sensorcell 114. Processor 210 controls the communications between the sensormodule 34 and the dispenser module 54, as well as externalcommunication. When given fill parameters and a “go” command, thecontrol processor 210 provides the intelligence to read the sensor celland command the dispenser module actuators to perform cartridge filling.The control processor 210 also communicates with a supervisory processor212 through a network interface. The supervisory processor 212 provideshigh level control of all the powder dispenser modules and sensor cells.

The controller of FIG. 17, except for supervisory processor, is repeatedfor each dispenser module 54 and associated sensor cell 114 in thesystem. In the above example of a 6×8 array of dispenser modules, thesystem includes 48 controllers. This arrangement provides individualcontrol and monitoring of powder dispensing into each cartridge.

In one embodiment, the powder dispenser module 54 is configured andcontrolled to accurately dispense 10.0 mg (milligrams) of powder in tenseconds. The average flow rate is 1.0 mg per second at an accuracy of+/−0.3 mg, or 3 percent. The control circuit makes at least 20 decisionsper second to fill at this flow rate. In other embodiments, the controlcircuit makes more or fewer than 20 decisions per second to achieve adesired accuracy. The feed wand geometry provides sufficient flowconsistency to achieve this performance. The feed wand breaks downpowder clumps into small agglomerate particles. The mechanically-fedagglomerate slurry has flow characteristics that allow the powder to behalted when the feed wand is stopped, with minimal powder overspill,which would cause overfilling of the cartridge.

The control circuit can provide the following controls and functions.

1. Wand speed is variable from 0.1 revolutions per second to 5revolutions per second in 50 different speeds.

2. The wand can be dithered while filling. In dithering, the wandalternately rotates clockwise then counterclockwise, such as for examplewith a two steps forward/one step backward, type of motion based upon aprogrammable dither factor. A “dither less than weight” function engagesthe dither motion when the fill weight is less than a selected weight. A“dither greater than weight” function engages the dither motion when thefill weight is greater than the selected weight. A “dither between”function engages the dither motion when the fill weight is between twoselected weights. A dither index is the selected rotational speed whiledithering. A dither weight is the selected weight to start or stopdithering, and a minimum dither time at the selected dither weight canbe selected. In some applications, dithering may not be utilized.

3. The control circuit can open and close the powder dispenser fillvalve.

4. The control circuit can tare the sensor cell and start a powderdispensing cycle, and can stop the powder dispensing cycle.

5. The control circuit can rake the powder in the powder dispenser witha sequence defined by rake time, dither time and speed.

6. A new load function starts a raking/dither cycle usually run afterloading the dispenser module with fresh powder. The rake time, dithertime and speed are specified.

7. Additional functions include automatically opening and closing thefill valve during a filling cycle, automatically raking the powder eachtime the valve closes, and automatically dithering the powder afterraking each time the valve closes.

8. A “stop-steps” function sets the number of steps to reverse rotatethe feed wand after reaching a target weight. This tends to pull thepowder flow back to prevent overfill and depends on the type of powdermorphology and relevant ambient humidity conditions.

9. A speed control function forces the feed wand to run at full speeduntil reaching a selected fill weight. At this trigger point,proportional control starts to reduce the wand speed in proportion tothe target weight minus the actual weight. This approach reduces thetotal fill time. For a nominal fill weight of 10 mg and a tolerance of+/−3 percent, any fill weight between 10.3 and 9.7 mg is acceptable.Since an overfilled cartridge must be discarded, filling is stopped assoon as possible after reaching the minimum weight in order to avoidpossible overfills. The minimum weight is set, for example, to 9.75 mg,which is slightly above the actual low limit of 9.70 mg. This isnecessary because when powder falls into the cartridge, peripheralforces such as inertia, aerodynamics, static, and magnetic field fluxcan cause temporary weight readings that are slightly higher than theactual powder weight. The reading settles to the actual weight over abrief time of a few tenths of a second. Setting the minimum weight to0.05 mg above the actual low limit reduces the risk of an underfilledcartridge.

10. Parameters associated with the fill cycle include the proportionalgain of the fill servo loop, the integral gain of the fill servo loopwhich is activated, for example, at 1.0 mg less than the target weight,and the maximum wand speed allowed during a fill cycle. The wand speedcan be controlled by specifying a speed index between 0 and 50. The wandspeed in revolutions per minute as a function of wand speed index has acharacteristic that is relatively linear for low values of wand speedindex and then increases dramatically to the maximum wand speed. Thischaracteristic provides finer control at lower speeds than at higherspeeds and permits the wand to be run much faster during the initial 70percent of the fill cycle to quickly fill the cartridge to 90 percent ofits fill weight. The maximum wand speed is typically about 5 revolutionsper second. Beyond that speed, there is a risk of packing the powder sotightly that the dispenser would have to be removed and cleaned torestore the original powder flow characteristics.

A dither factor controls reciprocation of the feed wand as it rotates,if dithering is enabled. In this embodiment, the ratio of forwardrotation to reverse rotation is two. Thus, the feed wand rotates 2nsteps forward and n steps backward, based on the value of the ditherfactor. Thus, for example, a dither factor of 500 represents 1000 stepsforward and 500 steps backward, whereas a dither factor of 1 represents2 steps forward and 1 step backward. In other embodiments, the ratio offorward rotation to reverse rotation can have a value different from twoand/or can be programmable.

11. A fill time servo control function adjusts the maximum index of wandspeed in proportion to the time spent at full speed during the last fillcycle. The time spent at full speed is a good indication as to how wellthe powder is flowing. If the actual time at full speed is greater thanthe setting, then the control increases the maximum wand speed index tospeed up the filling. Conversely, if the actual time at full speed isless than the setting, the maximum wand speed index is decreased tomaintain a consistent process time. While filling as fast as possibleappears desirable, there is a risk of packing the powder, clogging thedispensers or overfilling the cartridges.

The parameters of the powder dispenser module 54 are interrelated asfollows. Greater overshoot control is available when smaller particleagglomerate sizes are dispensed into the cartridge. Speeding up the wandincreases flow rates but compresses the powder into large agglomerates.Large agglomerates increase flow, but are more likely to overfill in thelast seconds of filling. A large powder reservoir saves dispenserloading time, but compresses the powder into large agglomerates andrequires more powder conditioning prior to filling. Dithering chops upthe large agglomerates for more accurate filling, but reduces the flowrate. Conditioning the powder prior to filling increases fillingconsistency, but adds to overall filling time.

An embodiment of a cartridge fill cycle is described with reference toFIGS. 18 and 19. The fill cycle is described with reference to anexample of filling the cartridge with a 10 mg dose of Technospheremicroparticles in 10 seconds. It will be understood that differentparameters can be utilized for different fill weights, different powdermorphologies, different fill times and different environmentalconditions. The cartridge fill cycle can be executed by controlprocessor 210 and dispenser controller 200.

The dispenser control processors in conjunction with the supervisorycomputer monitors all of these control factors against the fillingweight values, read 20 times per second, as the dispensers are fillingthe cartridges. This data, when compared against ideal dispense cycles,provides feedback to promote improved powder cohesivity, flowability,consistency, patient drug efficacy and overall quality control. It willbe understood that the weight values can be read more or fewer than 20times per second within the scope of the invention.

Referring to FIG. 18, control parameters for dispenser module operationmay be set in step 250. For example, initially, dithering is set to“off.” The valve control parameters can be set such that raking is setfor two seconds after a new powder load, the speed index is set to 44,auto-open is set to “on” and automatic rake after close is set to twoseconds. Fill parameters can include a setting of 8.8 mg at whichproportional control begins, the target fill weight can be set to 10.0mg, proportional gain can be set to 1.0, integral gain can be set to0.03, and the maximum wand speed index can be set to 41 (two revolutionsper second). The dither factor can be set to 50, and the fill time servocan be set to 10.0 seconds. A bipolar ionizer can be activated to chargeneutralize the powder dispenser module and the cartridge.

In step 254, the dispenser hopper 156 is filled with powder by operationof the powder transport system 32. Powder is delivered to array block 50by powder aerator 72. The powder is supplied through the channels inarray block 50 to each of the powder dispenser modules 54. When excesspowder passes through array block 50 and is sensed by the dispenser filllevel sensor in suction manifold 84, loading of the dispenser modules 54is complete, and the powder transport system is de-energized. Thedispenser hopper 156 can be raked during the hopper fill cycle to removelarge air gaps and inconsistencies in the powder bed.

The hopper assembly 74 is filled by the operator or other automaticinjection system. The flow assist mechanism rotates to breakup the newcompressed powder. The agglomerator rollers rotate to deliver largeagglomerate powder to the dump valve in the aerator 72. A dump valvelevel sensor signals that the dump valve is full to stop theagglomerator rollers. The blower assembly 70 rotates at approximately3500 rpm to cycle gas through the system. The pneumatic broom rotates inpreparation for powder delivery by the dump valve. The bypass valve isset to 50% to facilitate both powder and air stream gas transport.

The dump valve rotates in 10 degree per second increments to graduallydrop powder into the pneumatic broom chambers. As powder becomesavailable to the pneumatic broom, fine agglomerates are transported upthe risers and into the dispenser fill chamber. Most filling occurs inthe last dispenser positions at this time. After the dump valve cycle iscomplete, the crossover valve rotates to 0% bypass in 10 degree persecond increments to phase in maximum pneumatic broom pressure. Thistransports all but the heaviest agglomerates into the dispenser chamberand fills the middle rows of dispenser modules. Lastly, the blowerassembly 70 increases speed to 8000 rpm to transport the remainder ofthe powder from the pneumatic broom chamber to the first rows ofdispenser modules.

As these fill cycles continue, the dispenser hoppers become full. Theblower assembly 70 in combination with the bypass valve even out thedispenser bed height across the dispenser modules by scavenging powderfrom the high peaks, circulating the fine powder through the system anddepositing the powder into the low pressure areas of the powder bedbetween the peaks.

In step 258, a cartridge is positioned below the dispenser nozzle 158 onthe weight sensor cell. As described above, a tray of cartridges ispositioned between the array of powder dispenser modules 54 and thesensor module 34. In step 260, the cartridge is filled with theprescribed dose of powder. The fill cycle is described below inconnection with FIG. 19. In step 262, the fill valve is closed androtation of the feed wand is stopped.

In step 264, a determination is made as to whether the dispenser hopperrequires refilling. If the dispenser hopper requires refilling, theprocess returns to step 254. If the dispenser hopper does not requirerefilling, the process returns to step 256. In the present example, thedispenser hopper can be refilled after four 10.0 mg doses. It will beunderstood that refilling of the dispenser hopper can be initiated aftermore or fewer than four cartridge fill cycles, depending for example onthe capacity of the dispenser hopper and the quantity of powderdispensed on each fill cycle. The dispenser hopper is refilled in step254. If refilling is not required, the process proceeds with the fillcycle for the next cartridge in step 256. In the present example, thedispenser hopper contains enough powder for twenty 10.0 mg doses. Insome embodiments, the filling process is dependent upon the powderheight in the dispenser hopper to create a dry powder fluidic head andto assist in gravity-induced powder flow. Without an adequate fluidichead, the filling time increases beyond the fill time limit. Othertechniques may be used to determine that refilling of the dispenserhopper 156 is required. For example, if little or no powder is dispensedduring the cartridge fill cycle, it may be assumed that refilling ofdispenser hopper 156 is required.

An embodiment of the cartridge fill cycle is shown in FIG. 19. Aninitial operation is to tare the sensor cell in step 280. The tareoperation subtracts the empty cartridge weight from the sensor cellreading so that the sensor cell reads zero or near zero at the beginningof the fill cycle. The control circuit waits 0.5 second for the sensorcell to complete its tare cycle and proceeds with the fill operation ifthe sensor cell reads less than 0.02 mg. Otherwise, the tare cycle isrepeated.

In step 282, the fill valve 180 is opened. As described below, the fillvalve opening can be slightly offset from the dispenser nozzle 158 toensure consistent operation.

In step 284, the feed wand is rotated in the counterclockwise directionfor filling. Typically, actual filling starts after about 2 seconds, thetime needed to advance enough powder to restart powder flowing afterraking. Initially, the feed wand is rotated at the full speed specifiedduring dispenser module setup. The weight of the dispensed powder in thecartridge is monitored during filling.

In step 286, a determination is made as to whether the current sensedweight is greater than the selected weight at which proportional controlis initiated. In the example of a 10 mg dose, the selected weight can be8.8 mg. If the sensed weight is not greater than the selected weight,the process returns to step 284 and rotation of the feed wand continuesat full speed. If the sensed weight is greater than the selected weight,servo control of wand speed is utilized in step 288. An initial error isdetermined as the target weight minus the selected weight at which servocontrol is initiated. In the above example, the initial error is10.0−8.8=1.2 mg. The wand speed is controlled according to:New wand speed index=((current error/initial error)*proportionalgain*max index)+(integral gain*elapsed time).

In this embodiment, the control circuit sets the wand speed based on thecurrent error 20 times per second. The current error is determined asthe target weight minus the current sensed weight. For a current errorof 0.6 mg, which is one-half the initial error in the above example, thewand speed is reduced from the max index of 41 to an index of 20. Due tothe nonlinearity of the index-speed curve, the actual wand speed is lessthan half of the initial speed. As noted above, the index-speed curve islinear to zero where the most control is needed. The proportional gainvalue allows the amount of speed change as a function of error to bevaried. The elapsed time is turned “on” when the current sensed weightis greater than the target weight minus 1.0 mg. The proportional errorequation reduces the wand speed based on a fixed ratio of actual todesired weight. There are times at very low speed, when nearing thetarget weight, that the wand speed is inadequate to produce powder flow.If left alone, the fill cycle would run overtime and fail to completethe target weight. The integral gain factor increases the speed byaccumulating elapsed time and multiplying elapsed time by the integralgain factor. This factor increases the new wand speed and forces thewand to rotate faster to overcome the filling stall.

Referring again to FIG. 19, the current sensed weight is compared withthe minimum weight in step 290. If the current sensed weight is lessthan the minimum weight, servo control of the wand speed continues instep 288. If the current sensed weight is equal to or greater than theminimum weight, the current sensed weight is compared with the maximumweight in step 292. If the current sensed weight is greater than themaximum weight, the cartridge is determined to be overfilled in step294. If the current sensed weight is not greater than the maximumweight, the fill cycle is complete and the process returns to step 262in FIG. 18.

In step 262, the control circuit can adjust the servo. If the fill timewas greater than 11 seconds, the control circuit can increase the maxspeed index by one. If the fill time was less than nine seconds, thenthe control circuit can decrease the max speed index by one. Thiscontrol attempts to maintain a consistent fill time of 10 seconds.

Preferably, valve member 190 is positioned such that valve opening 191is offset with respect to the lower end of tapered conduit 154 when fillvalve 180 is in the open position. More particularly, valve member 190is offset such that valve opening 191 is post-positioned relative totapered conduit 154. That is valve opening 191 is offset toward theclosed position of the valve. In addition, valve member 190 is rotatedin one direction when opening and closing the valve to compensate forany hysteresis in the drive train. Thus, for example, valve member 190can be rotated clockwise to open the valve and can be rotated furtherclockwise to close the valve. This operation reduces the risk ofinconsistent filling or overfilling that can result from uncontrolledoffset between valve member 190 and tapered conduit 154 in the openposition.

Any offset between valve opening 191 and tapered conduit 154 in the openposition produces a small shelf on the top of valve member 190 that canaccumulate powder. If the valve opening 191 is pre-positioned relativeto tapered conduit 154, any powder on the shelf is dumped when the valveis closing, thus potentially overfilling the cartridge. When valveopening 191 is post-positioned relative to tapered conduit 154, thevalve closes without dumping any powder from the shelf. The powder isdumped when the valve is opened for the next cartridge, and the dumpedpowder is measured by the sensor cell.

The powder dispenser module 54 and its operation have been described inconnection with embodiments for dispensing a specified quantity ofTechnosphere microparticles in a specified time. It will be understoodthat a variety of different dispenser module structures and operatingprotocols can be utilized within the present invention. For example, thefeed wand can utilize different structures, such as different sparconfigurations, different wire configurations, and in some embodimentswires may not be required. Different numbers of helix wires and chevronwires can be utilized. Different discharge elements can be utilized. Thefeed wand can utilize a different feed mechanism, such as a screwmechanism, for dispensing powder. Any suitable fill valve mechanism canbe utilized to control dispensing of powder. Regarding operation, anyoperation protocol that achieves desired operating parameters can beutilized. For example, any suitable motion of the feed wand, such asrotation, reciprocation, or vibration, can be utilized. The speed ofmotion can be fixed or variable, or a combination thereof. Dithering,proportional control, integral control, and other control techniques canbe utilized separately or in combination as needed. The sensor modulecan be configured to provide sensed values at any desired rate, withinthe capabilities of the sensor module. In general, powder dispensermodule 54 should have a compact structure to permit mounting in an arrayas described above and should be configured to dispense a desiredquantity of powder in a specified time interval in response to a controlcircuit that receives sensed values from a sensor module, such as theweight sensor in the embodiment described above.

As shown in FIGS. 20 and 21, sensor module 34 can include sensorassemblies 110 mounted in sensor housing 100. In the illustratedembodiment, each sensor assembly 110 includes two sensor cells 114. Thesensor assemblies 110 are mounted in sensor housing 100 so that sensorcells 114 are positioned to weigh cartridges 20 in cartridge tray 22. Inone embodiment, sensor cells 114 are mounted in a 6×8 array on one inchcenters. In this embodiment, 24 sensor assemblies 110, each includingtwo sensor cells 114, are utilized to provide an array of 48 sensorcells.

Each sensor assembly 110 has a vertical configuration wherein two sensorcells are packaged together. Weight sensing mechanical components arelocated at the top of the assembly, electronic circuitry is locatedbelow the mechanical components and an electrical connector 300 islocated at the bottom of the sensor assembly 110.

Sensor housing 100 includes a sensor locating plate 310, a sensorenclosure 312, a sensor tray 314 and a guide pin assembly 316. Locatingplate 310 includes an array of openings that match the positions ofcartridges 20 in cartridge tray 22, so that the sensor cells 114 areaccurately positioned with respect to cartridges 20. Guide pin assembly316 permits locating plate 310 to be positioned on sensor assemblies 110without damaging the sensitive probes 112 or the sensor cells. Sensortray 314 can include an arrangement of dividers for positioning sensorassemblies 110 in sensor module 34.

Sensor module 34 further includes sensor backplanes 330 havingconnectors 332 for engaging the electrical connectors 300 of sensorassemblies 110. In the embodiment of FIGS. 20 and 21, sensor module 34includes two backplanes 330, each having 12 connectors 332 toaccommodate a total of 24 sensor assemblies 110. Each sensor backplane330 can include control circuitry for processing signals from sensorassemblies 110 and for communicating with powder dispenser modules 54during cartridge fill operations.

Sensor module 34 can be provided with an arrangement for cooling sensorassemblies 110, including a sensor cooling grid 340, a sensor coolinghousing 342 and sensor cooling manifolds 344 and 346. Cooling air can bedirected through cooling manifolds 344 so that forced air cooling isprovided to the lower portion of sensor module 34 which containselectrical circuitry. In the embodiment of FIGS. 20 and 21, coolingmanifolds 344 are attached to sensor tray 314 and cooling manifolds 346are attached to cooling housing 342. With this arrangement, cooling aircirculates into the sensor module 34 through cooling manifolds 344,circulates through sensor tray 314 and then downwardly into coolinghousing 342, and is exhausted through cooling manifolds 346. In anothercooling arrangement, cooling manifolds 346 are attached to sensor tray314 so that cooling air is directed through sensor tray 314. Unusedopenings in sensor tray 314 can be closed by cover plates 348. Each ofcooling manifolds 344 and 346 can include internal passages whichprovide uniform air flow through the sensor module. In addition, coolingmanifolds 344 and 346 can include temperature sensing elements formonitoring of sensor module temperature.

A first embodiment of the weight sensor probe which provides aninterface between the weight sensor cell and cartridge 20 is shown inFIG. 22. Probe 112 includes a main body 360 including a post 362 thatengages the sensor cell, a head 364 and a cup 366 that accumulates dustand stray powder particles. Probe 112 further includes a dust skirt 370that deflects dust and powder particles away from the sensor cell andpins 372 for engaging and supporting cartridge 20. The three pins 372are equally spaced at 120 degree intervals and are designed toelastically flex and then return to their original positions. Inaddition, the pins are designed to buckle in an overload condition toprotect the sensor cell. In the embodiment of FIG. 22, pins 72 areremovable for pin height changes for different cartridge tray designs.The small cross-sectional area of the pins reduces the aerodynamiceffects of thermal currents which can add bias load forces to precisemicrogram weight measurements.

A second embodiment of the weight sensor probe which provides aninterface between the weight sensor cell and cartridge 20 is shown inFIG. 23. A probe 112 a includes a main body 380, including a post 382, ahead 384 and a cup 386. Cup 386 accumulates dust and stray powderparticles. A dust skirt 390 deflects dust and powder particles away fromthe sensor cell. In the embodiment of FIG. 23, probe 112 a includes pins392 that are formed integrally with head 384. Each of pins 392 isreinforced with a radial gusset. This configuration adds structuralrigidity to the vertically cantilevered lift pins. This configurationalso reduces vibration and displacement at the tips of the pins, thusdamping the tuning fork effect.

A first embodiment of powder aerator 72 is shown in FIGS. 24-27 and28A-28C. A second embodiment of powder aerator 72 is shown in FIGS.29-32. Powder aerator 72 includes a manifold block 500 which defines gasinlet 78, powder inlet 80 and powder output ports 82. As describedabove, gas inlet 78 is connected via tube 76 to blower assembly 70,hopper assembly 74 is mounted to powder inlet 80, and powder outputports 82 are connected to respective channels in array block 50. Powderaerator 72 can include a pneumatic broom 510 to deliver powder throughriser tubes 512 to powder output ports 82 and a dump valve 520 to supplya quantity of powder from powder inlet 80 to the pneumatic broom 510. Inthe embodiment of FIGS. 24-27 and 28A-28C, four riser tubes 512 inmanifold block 500 connect pneumatic broom 510 to powder output ports82. Powder aerator 72 further includes a crossover valve 524 thatdirects transport gas received through gas inlet 78 to pneumatic broom510 and to a bypass manifold 526 in a desired proportion. Transport gasdirected through bypass manifold 526 is caused to flow through powderoutput ports 82 to array block 50 so as to transport powder to thepowder dispenser modules 54 mounted in each channel of array block 50.

Pneumatic broom 510 includes a generally cylindrical aerator tube 530having a hollow interior and provided with discharge nozzles 532.Aerator tube 530 is located in a bore in manifold block 500. Dischargenozzles 532 can be formed in a helical pattern on aerator tube 530 andcan be approximately tangential with respect to a cylindrical surface ofaerator tube 530. Dividers 534 are spaced apart along aerator tube 530and define annular chambers 542 corresponding to respective riser tubes512. In addition, pneumatic broom 510 includes paddles 590 affixed todividers 534 and spaced around the annular chambers 542. The combinationof discharge nozzles 532 and paddles 590 provides effective transport ofa powder slurry into array block 50. A flow director 536 attached to oneend of aerator tube 530 includes vanes to help to break up clumps ofpowder and to direct transport gas from crossover valve 524 to thehollow interior of aerator tube 530. An aerator core 538 has a contourto assist in equalizing flow of transport gas through discharge nozzles532. A motor 540 causes aerator tube 530 and flow director 536 to rotatewithin manifold block 500. Motor 540 can have variable speed and rotatespneumatic broom 510 at relatively high speed, for example 3500 rpm, fortransport of a powder slurry.

Dump valve 520 includes a cylindrical core 550 having diametricallyopposed cavities 552. Core 550 is mounted in a bore in manifold block500 above pneumatic broom 510 and is connected to a motor 554 forrotation about its central axis. Core 550 is positioned by motor 554with one of the cavities 552 facing upwardly toward powder inlet 80.Powder is supplied by hopper assembly 74 through powder inlet 80 so asto fill or partially fill cavity 552. Then, core 550 is rotated by 180°,causing the powder to be dumped into the annular chambers 542 aroundaerator tube 530. The maximum quantity of powder supplied in a singleoperation of dump valve 520 is defined by the volume of cavity 552.

Crossover valve 524 includes a valve member 560 mounted in a bore inmanifold block 500 and a valve actuator 562 to rotate valve member 560about its central axis. Valve member 560 can be configured as a hollowcylinder having an inlet port 564 and outlet ports 566 and 568 atselected circumferential positions. The ports 564, 566 and 568 can beprovided with vanes to block and break up powder clumps. By appropriateadjustment of valve member 560, transport gas received through gas inlet78 can be directed in desired proportions through pneumatic broom 510and through bypass manifold 526. In one embodiment, crossover valve 524is adjusted during delivery of powder to array block 50. In anotherembodiment, crossover valve 524 has a fixed position during delivery ofpowder to array block 50.

Powder aerator 72 can further include flow straighteners 570 andcontoured flow element 572 to assist in providing a uniform flow oftransport gas through each of the powder output ports 82. Each outputport 82 can be configured as a discharge cavity that matches the inletend of one of channels 60 a-60 h. Bypass manifold 526 supplies transportgas to the upper part of each discharge cavity, and each riser tube 512supplies aerated powder upwardly into the flow of transport gas in thedischarge cavity, as best shown in FIG. 28A.

The powder aerator 72 serves as the interface between the hopperassembly 74, the array block 50 and the blower assembly 70. Powderaerator 72 receives fresh powder from hopper assembly 74 and receivesrecirculated powder from blower assembly 70. The fresh powder isreceived through dump valve 520, and the recirculated powder is receivedthrough gas inlet 78 and is distributed by crossover valve 524 topneumatic broom 510 and bypass manifold 526 according to the position ofcrossover valve 524.

The second embodiment of powder aerator 72 shown in FIGS. 29-32 issimilar to the powder aerator shown in FIGS. 24-27 and 28A-28C, exceptas follows. As best shown in FIGS. 31 and 32, pneumatic broom 510similarly includes dividers 534 a which are spaced apart along aeratortube 530 and define annular chambers corresponding to respective risertubes in manifold block 500. The pneumatic broom 510 in the secondembodiment does not include paddles spaced around the annular chambers.In addition, the powder aerator of FIGS. 29-32 is provided with a motor540 a which rotates pneumatic broom 510 at relatively low speed, forexample 1 to 10 rpm, for transport of a powder aerosol.

Components of powder aerator 72 include pneumatic broom 510, dump valve520 and crossover valve 524. In addition, bypass manifold 526, flowelement 572 and flow straighteners 570 are used to equalize gas flowwithin each channel of array block 50. The pneumatic broom 510, thecrossover valve 524 and the dump valve 520 are motor operated and arecontrolled by a system control computer.

The crossover valve 524 channels the incoming transport gas in twodirections: into the bypass manifold 526 and into the pneumatic broom510. The rotary cylindrical valve has longitudinal slots to channelflows while maintaining a relatively constant hydraulic loss, thuspromoting a stable discharge.

The pneumatic broom 510 has several elements. The intake channelingvanes on flow director 536 change the direction of the incomingtransport gas in an efficient, low-loss manner, while creating animpactor system that blocks and obliterates stray agglomerates beforethey clog downstream discharge nozzles 532. Tangential gas dischargenozzles 532, preferably having a double helix configuration, arearranged along the length of aerator tube 530. The pneumatic broom 510is divided into four annular chambers 542. The drug powder that issupplied from the dump valve 520 is aerated in annular chambers 542. Thetangential discharge nozzles 532 effectively aerate and sweep the drugpowder from the chamber walls. The crossover valve 524 allows the twotransport gas streams to be controlled inversely, i.e. one can beincreased while the other is reduced. This control function allows thedrug powder to be tumbled within annular chambers 542 to form thenatural average agglomerate size. Then the transport gas flow can besteadily increased to transport the aerated powder slurry up riser tubes512 and into the channels of array block 50, which fills the array blockchannels in a controlled particle deposition process. This transportprocess takes advantage of the undesirable powder morphology ofnaturally agglomerating powders and coerces them into an agglomeratestate that allows them to be effectively pneumatically transported.

The riser tubes 512 intersect the discharge cavity of each output port82. At this juncture, the horizontal transport gas deflects the uprisingemerging powder slurry and downdrafts it into the channels of arrayblock 50. This process creates the conditions for the controlledparticle deposition process.

The powder aerator 72 receives a known quantity of powder from thehopper assembly 74. The powder is collected in the dump valve 520. Thedump valve 520 isolates the transport gas from the hopper assembly 74.In addition, the dump valve 520 transfers the powder through this gasinterlock and into the pneumatic broom 510. The dump valve 520 can havean optional capability of making a coarse weight measurement of theinitial drug powder deposited into the system from hopper assembly 74.The weight measurement can be performed by a load cell positioned incavity 552 of dump valve 520. The coarse weight measurement can be usedas a feedback control to hopper assembly 74 as well as additional datato monitor bulk powder dispensing rates.

The pneumatic broom 510 fluidizes, disperses and entrains drug powdersin a transport gas in annular chambers 542. The chambers 542 aresupplied with transport gas by multiple tangential discharge nozzles 532in a helical configuration. The helical configuration can include one ormore helices, such as a double helix. In addition, the pneumatic broom510 includes gas channeling vanes in flow director 536 that efficientlydirect gas into the aerator tube 530 and act as impactors to reducelarge agglomerates before they reach the discharge nozzles 532.

The crossover valve 524 divides the incoming transport gas betweenpneumatic broom 510 and bypass manifold 526. The crossover valve 524 isconfigured to inhibit any eddy vortex flow conditions within a compactdesign. The valve has slot flow ports to optimize and control the flowof gas. The crossover valve is used to control the transport of theaerated, agglomerated powder slurry into the channels 60 a-60 h of arrayblock 50.

Contoured flow element 572 is placed within bypass manifold 526 toenhance the conduit flow geometry. As the bypass gas flows from thecrossover valve 524 and into bypass manifold 526, it is preferable tocreate isokinetic flow patterns to inhibit the formation of tripped flowor eddy flow stagnation zone conditions.

Flow straighteners 570 include vanes which regulate gas flow byrestricting and straightening gas flow as it discharges into thedischarge cavity 580. By altering the spacing between vanes, it ispossible to achieve uniform flow rates through each of the channels 60a-60 h of array block 50.

A first embodiment of hopper assembly 74 is shown in FIGS. 33 and 34. Asshown in FIGS. 33 and 34, hopper assembly 74 includes a hopper body 600,which defines a powder reservoir 610, for holding a supply of powder,and a powder outlet 612, which engages the powder inlet 80 of powderaerator 72. The hopper assembly 74 can be provided with a hinged cover614 and a flow assist mechanism 620. Flow assist mechanism 620 caninclude helical coil 622 located within powder reservoir 610 and a motor624 to rotate coil 622. Hopper assembly 74 can further include agranulator 630 in a lower portion of powder reservoir 610. Granulator630 can include a first agglomerator roller 632 coupled to a first motor634 and a second agglomerator roller 636 coupled to a second motor 638.Each of agglomerator rollers 632 and 636 is provided with a plurality ofpins 640 extending radially from the respective roller. In oneembodiment, the locations of pins 640 on each of rollers 632 and 636define one or more helical patterns. In addition, agglomerator rollers632 and 636 can have hollow centers and can be provided with air holesthat connect to the hollow centers. Gas connectors 650 at the ends ofrollers 632 and 636 can be connected to a source of pressurized air. Airflow through the holes in rollers 632 and 636 assists in aerating thepowder being supplied to the system.

In operation, after the powder reservoir 610 has been filled to thelevel of the hopper level sensor, first and second agglomerator rollers632 and 636 rotate, causing powder agglomeration and discharge of theagglomerated powder through powder outlet 612 to powder aerator 72. In apreferred embodiment, agglomerator rollers 632 and 636 rotate inopposite directions, with the tops of rollers 632 and 636 rotatingtoward each other. However, operation is not limited in this regard.Agglomerator rollers 632 and 636 can be rotated continuously, withreciprocating motion or with a combination of continuous andreciprocating motion, and can be reversed. The rotation protocol dependson powder morphology. Granulator 630 produces powder agglomerates in adesired size range to enhance powder flow from hopper assembly 74 intopowder aerator 72.

A second embodiment of hopper assembly 74 is shown in FIGS. 35 and 36.The hopper assembly of FIGS. 35 and 36 is similar to the hopper assemblyof FIGS. 33 and 34, except as follows. In the hopper assembly of FIGS.35 and 36, the flow assist mechanism is not utilized. In addition,granulator 630 is implemented with agglomerator rollers 632 a and 636 a,each of which is provided with a plurality of spaced-apart disks 660mounted to shafts of the respective rollers. The disks 660 can beprovided with notches 662 which assist in moving the powder downwardlythrough reservoir 610. The disks of roller 632 a may be intermeshed withthe disks of roller 636 a.

Bulk powder can be introduced into powder reservoir 610 through theopening at the top of hopper body 600 with cover 614 open. In the secondembodiment of hopper assembly 74 shown in FIGS. 35 and 36, a powderslurry can be introduced into powder reservoir 610 through a fitting 670on an angled portion of hopper body 600. Fittings 672 mounted in theupper portion of hopper body 600 provide an exhaust for transport gasintroduced through fitting 670 with the powder slurry.

The hopper assembly 74 is the main powder reservoir and is the stage atwhich powder is introduced into the powder delivery system 32. Thehopper assembly 74 is designed for highly cohesive powders such asTechnosphere microparticles. The granulator 630 produces powderagglomerates in a finite size range. This preconditioning enhances thepowder aeration and entrainment characteristics by creating a moreuniform polysize agglomerated powder blend. In addition, the process ofpowder granulation aerates and mixes the powder that is normallycompressed by gravity when stacked inside powder reservoir 610.

In the mid-region of powder reservoir 610, flow assist mechanism 620forces the powder to avalanche downward or fall toward granulator 630.The need for flow assist mechanism 620 is contingent on the level ofpowder cohesivity. The effect can become more apparent when the drugconcentration is increased, such as an increase in protein content thatmakes the particles more viscous or sticky.

A first embodiment of blower assembly 70 is shown in FIGS. 37 and 38. Asshown in FIGS. 37 and 38, components of blower assembly 70 can include avariable speed blower 700 and a cyclone separator 702. Blower 700includes a blower motor 704 supported by a motor mount 706 and animpeller 708 mounted in a blower housing 710. Blower housing 710 has adischarge port 712 for supplying transport gas through tube 76 to powderaerator 72. Tuned suction manifold 84 is mounted to the lower end ofblower housing 710. As described above, transport gas is recirculatedfrom array block 50 to blower assembly 70. Suction manifold 84 includesinlet ports 714 a, 714 b, 714 c and 714 d, which are connected torespective channels in array block 50. Cyclone separator 702 includes acylindrical housing section 84 a of suction manifold 84, which ismounted to blower housing 710, and a cyclone vessel 720 mounted belowsuction manifold 84. Cyclone separator 702, which serves as agas-particle separation device, receives powder agglomerates that passthrough array block 50 without being delivered to powder dispensermodules 54.

A porous induction rod 724 is located within the center of cyclonevessel 720 and is connected to a gas conditioning system 730, as shownin FIG. 41 and described below. The gas conditioning system 730 suppliesconditioned gas through porous induction rod 724 to establish aprecisely-controlled relative humidity within the powder delivery system32.

In other embodiments, conditioned gas can be pulsed by a valve into theclosed loop system from a source such as a pure water vapor source or asteam source. The loop relative humidity is controlled by sensing thegas in a small bypass loop that is connected to a sensing chamber fortemperature, pressure and relative humidity sensors. The bypass loop canbe located between the blower discharge port 712 and the tuned suctionmanifold 84. In further embodiments, the pulsed valve system can beconfigured as a dual port system that allows an amount of conditionedgas to be pulsed into the closed loop system, and a compensating orequal amount of transport gas to be discharged out of the closed loopsystem.

A second embodiment of blower assembly 70 is shown in FIGS. 39 and 40.The blower assembly of FIGS. 39 and 40 is similar to the blower assemblyof FIGS. 38 and 39, except as follows. In the blower assembly of FIGS.39 and 40, the cyclone separator is not utilized. Instead, a vaneseparator 750 is positioned in the housing section 84 a of suctionmanifold 84 on the suction side of the blower. The vane separator 750,which serves as a gas-particle separation device, has a cylindricalconfiguration of vanes 752 separated by vertical slots for separation ofheavy particles from the transport gas. A tangential flow of transportgas outside vane separator 750 removes heavier particles, while lighterparticles and the transport gas move to the interior of vane separator750 and then to impeller 708. The induction rod 724 is positioned in theinterior of vane separator 750 in the second embodiment of blowerassembly 70.

The powder transport system 32 in the present embodiment is configuredas a closed loop system where excess particles and agglomerates areextracted from the recirculating gas loop to inhibit particle cloggingof the powder aerator discharge nozzles 532. This is accomplished by thecyclone separator 702, the vane separator, or any other gas-particleseparation device.

The powder transport system 32 is configured with a secondary processgas loop between the gas-particle separation device and the dischargeport 712 of blower 700. This control loop can introduce secondaryconditioned gas to regulate environmental parameters of the primaryrecirculating transport gas, such as temperature, pressure, relativehumidity, electrostatic levels, ion charge concentrations, gas elementmixtures, aerosol fine particle seeding, etc.

The closed-loop powder delivery system 32 is driven by blower assembly70, which is a hybrid of an impulse impeller blower coupled to theoutlet side of a cyclone separator or other gas-particle separationdevice. The blower assembly 70 forms the transport gas prime mover andincludes a self-cleaning powder agglomerate filtration system. Inaddition, the transport gas is conditioned by the secondary process loopwhich controls the gas properties of the primary process loop. These twoloops are nested together within the blower assembly 70. The blowerassembly 70 includes impeller 708 which has a paddle wheel configurationwith scroll curves between each impeller blade. The paddle wheelimpeller configuration produces dynamic shock waves in the form ofpressure pulses down tube 76 and into powder aerator 72. These shockwaves assist in the breakup, aeration and dispersion of compressed drugpowder.

The blower has a variable speed capability and is driven by blower motor704. When the motor 704 is operated beyond normal operating speeds, thetransport gas acts as a recirculating gas scrubber that assists inremoving residual powder from the closed loop conduit channels.

A schematic block diagram of gas conditioning system 730 is shown inFIG. 41. Gas conditioning system 730 includes a secondary gas treatmentloop that is distinct from the closed loop system for recirculation oftransport gas and delivery of powder to array block 50. A portion of therecirculating transport gas is diverted to the secondary gas treatmentloop near discharge port 712 of blower assembly 70. The conditioned gasis reintroduced into the recirculating transport gas loop throughinduction rod 724. The gas conditioning system 730 includes a vaporgenerator 800, coupled to a water supply 802, for rapidly generatingwater vapor, a desiccator 810 for reducing the relative humidity of thetransport gas, valves 812 and 814 for selecting vapor generator 800 ordesiccator 810, and filters 820 and 822.

The relative humidity of the transport gas can be measured by a sensor,such as the sensor chamber described below, positioned to sense thetransport gas. When the relative humidity of the transport gas is to beincreased, valves 812 and 814 are connected to vapor generator 800.Vapor generator 800 includes a bubble generator and flash evaporatorheaters for rapidly producing water vapor. The diverted transport gas inthe secondary loop passes through filter 820, vapor generator 800 andfilter 822, thus returning gas with increased relative humidity toinduction rod 724. When the relative humidity of the transport gas is tobe decreased, valves 812 and 814 are connected to desiccator 810. Thediverted transport gas in the secondary loop passes through filter 820,desiccator 810 and filter 822, thus returning gas with reduced relativehumidity to induction rod 724.

Transport gas conditioning is achieved by introducing a processtreatment gas into the inner core of the cyclone vessel 720. Theconditioned gas is introduced into the vessel at the end of inductionrod 724. Induction rod 724 is fabricated from a sintered metal or aporous plastic polymer which allows the conditioned gas to evenly mixinto the recirculating transport gas without producing water droplets orslug flow conditions. The process treatment gas loop is balanced by areturn takeoff branch line on the discharge side of blower 700. Aportion of the cyclone separator 720 or housing section 84 a can befabricated from glass for visual inspection of collected drug powders.If the collected powder is salvageable, it can be reintroduced into thehopper assembly 74, or it can be discarded.

The control of the humidification of powder during operation of thepowder transport system is complicated by the fact that the exposedsurface area of the powder changes during the transport process. Thepowder is initially prepared in the agglomerated state. However, as thepowder breaks down and disperses during gas transport, its exposedsurface area increases significantly, in turn causing rapid moistureuptake. In order for a humidification process to keep up with andcontrol this rapid dehydration of the transport gas loop, the gastreatment system must be capable of rapid forced hydration.

The cyclone separator 702 has an integral tuned intake manifold thatmerges into the cyclone body with minimal hydraulic loss. The blowerassembly has a large flow range and can serve as a system powderscrubber. The blower is equipped with a paddle wheel-like impellerhaving scrolled, curved surfaces between each paddle to efficientlytransport fine powder aerosols and to inhibit powder reagglomeration andcaking. The paddle wheel-like impeller directs dynamic shock waves intothe powder aerator 72 to assist in the fluidization of drug powders. Theblower assembly 70 includes a gas conditioning system where a secondarygas treatment loop is introduced into the unit through induction rod 724within the cyclone vessel. The gas conditioning system can control manygas parameters, such as relative humidity and temperature, ion staticcontrol, fine particle seeding, trace element seeding, gas catalystactivation, gas/light sterilization control, etc.

An embodiment of a sensor chamber 850 for sensing the condition of thetransport gas in the powder transport system is shown in FIGS. 42 and43. Transport gas, with powder removed to the extent that is practical,is circulated through sensor chamber 850 in parallel with the powdertransport system. The sensor chamber 850 contains sensors for sensingtransport gas parameters, such as relative humidity and temperature, topermit transport gas conditioning as described above.

Sensor chamber 850 receives transport gas through an inlet tube 852connected to blower housing 710 of blower assembly 70 and outputstransport gas through an outlet tube 854 connected to suction manifold84. Each of inlet tube 852 and outlet tube 854 is insulated and may beconfigured as inner and outer tubes separated by spaced-apart rings.Inlet tube 852 may be connected to blower housing 710 perpendicular tothe direction of transport gas flow to limit intake of powder intosensor chamber 850.

As shown in FIG. 43, sensor chamber 850 may include an upper housing 856and a lower housing 858 having an interior volume that is roughlyequivalent to the interior volume of array block 50. The sensor chamber850 may include a relative humidity sensor 860, a temperature sensor 862and a pressure sensor 864. In the embodiment of FIGS. 42 and 43,relative humidity sensor 860 includes a temperature sensor, whichpermits cross-checking against the temperature values sensed bytemperature sensor 862. A discrepancy in readings can indicate that thesensors are caked with powder and therefore not providing accuratesensing. An air baffle 866 is mounted in lower housing 858. The sensorchamber 850 provides accurate sensing of the conditions of the transportgas in the powder transport system.

A pictorial representation of the powder fill and assembly process foran inhaler cartridge is shown in FIG. 44. A cartridge bottom 900introduced into the system in a cartridge tray and is positioned onweight sensor probe 112 a for filling. Cartridge bottom 900 is filledwith drug powder by powder dispenser module 54 as described in detailabove. After filling, a cartridge top 902 is snapped onto cartridgebottom 900 to provide a complete cartridge 910 ready for sealedpackaging.

As noted above, the powder dispensing and sensing apparatus of thepresent invention can be utilized for filling different types ofcontainers. In another embodiment, the powder dispensing and sensingapparatus is used for filling a compact inhaler as described in U.S.Pat. No. 6,923,175 issued Aug. 2, 2005 to Poole, et al. As illustratedin FIG. 45, a cartridge bottom 920 of the compact inhaler is positionedon weight sensor probe 112 a for filling. Cartridge bottom 920 is filledwith drug powder by powder dispenser module 54 as described above. Then,a cartridge top 922 is attached to cartridge bottom 920 and a mouthpiecehousing 924 is fastened to the cartridge assembly. Finally, a dust cover930 is snapped over the mouthpiece housing 924 to provide a completecompact inhaler 932 ready for sealed packaging.

Having thus described several aspects of at least one embodiment of thisinvention, it is to be appreciated various alterations, modifications,and improvements will readily occur to those skilled in the art. Suchalterations, modifications, and improvements are intended to be part ofthis disclosure, and are intended to be within the spirit and scope ofthe invention. Accordingly, the foregoing description and drawings areby way of example only.

1. A powder transport system comprising: a powder dispenser assembly todispense powder into cartridges; a blower assembly to move a transportgas; and a powder aerator to deliver powder entrained in the transportgas to the powder dispenser assembly.
 2. A powder transport system asdefined in claim 1, further comprising a suction manifold to return thetransport gas to the blower assembly, wherein the powder transportsystem comprises a gas transport loop.
 3. A powder transport system asdefined in claim 2, further comprising a transport gas conditioningsystem.
 4. A powder transport system as defined in claim 3, wherein thetransport gas conditioning system is configured to control relativehumidity in the gas transport loop.
 5. A powder transport system asdefined in claim 2, further comprising a hopper assembly to supplypowder to the powder aerator.
 6. A powder transport system as defined inclaim 5, wherein the hopper assembly includes a hopper body defining apowder reservoir and a granulator in a lower portion of the powderreservoir.
 7. A powder transport system as defined in claim 6, whereinthe granulator comprises first and second agglomerator rollers and firstand second motors to rotate the first and second agglomerator rollers,respectively.
 8. A powder transport system as defined in claim 7,wherein each of the agglomerator rollers is provided with a plurality ofpins.
 9. A powder transport system as defined in claim 7, wherein eachof the agglomerator rollers is provided with a plurality of spaced-apartdisks, the disks of the first and second agglomerator rollers beinginterdigitated.
 10. A powder transport system as defined in claim 1,wherein the powder dispenser assembly comprises: an array blockincluding an array of vertical ports and horizontal channelsintersecting respective rows of the vertical ports; and powder dispensermodules mounted in respective vertical ports of the array block, each ofthe powder dispenser modules having a powder inlet communicating withthe channel in the array block, wherein powder delivered to the channelsin the array block is dispensed by each of the powder dispenser modules.11. A powder transport system as defined in claim 10, wherein eachchannel in the array block passes through the array block.
 12. A powdertransport system as defined in claim 10, wherein the powder inlets ofthe powder dispenser modules are aligned with the channels in the arrayblock so that powder delivered to the channels in the array block passesthrough powder inlets to downstream powder dispenser modules.
 13. Apowder transport system as defined in claim 1, wherein the powderaerator comprises: a manifold block defining a powder inlet, powderoutput ports and a transport gas inlet; a pneumatic broom to deliverpowder to the powder output ports; and a dump valve to supply a quantityof powder from the powder inlet to the pneumatic broom.
 14. A powdertransport system as defined in claim 13, wherein the powder aeratorfurther comprises a bypass manifold coupled to the powder output portsand a crossover valve to direct selected portions of the transport gasfrom the transport gas inlet to the pneumatic broom and to the bypassmanifold.
 15. A powder transport system as defined in claim 14, whereinthe powder aerator further comprises flow straighteners and a contouredflow element to assist in providing a uniform flow of the transport gasthrough the powder output ports.
 16. A powder transport system asdefined in claim 13, wherein the manifold block further defines risertubes connecting the pneumatic broom to the powder output ports.
 17. Apowder transport system as defined in claim 13, wherein the pneumaticbroom includes a hollow aerator tube having discharge nozzles thereon.18. A powder transport system as defined in claim 17, wherein thepneumatic broom further comprises one or more dividers, which defineannular chambers.
 19. A powder transport system as defined claim 18,wherein the pneumatic broom further comprises one or more paddles ineach of the annular chambers.
 20. A powder transport system as definedin claim 1, wherein the blower assembly comprises; an impeller to movethe transport gas; an impeller motor to rotate the impeller; a blowerhousing enclosing the impeller and having a discharge port for thetransport gas; a manifold to receive the transport gas; and agas-particle separation device to accumulate agglomerates entrained inthe transport gas.
 21. A powder transport system as defined in claim 20,wherein the gas-particle separation device comprises a cyclone separatordisposed between the manifold and the impeller.
 22. A powder transportsystem as defined in claim 20, wherein the gas-particle separationdevice comprises a vane separator disposed between the manifold and theimpeller.
 23. A powder transport system as defined in claim 20, furthercomprising an induction rod to induce conditioned transport gas into thegas-particle separation device.
 24. A powder transport system as definedin claim 3, wherein the transport gas conditioning system comprises asensor chamber coupled in parallel with the gas transport loop, thesensor chamber including at least one sensor to sense a parameter of thetransport gas, and a gas conditioning element responsive to the sensedparameter to condition the transport gas.
 25. A powder transport systemas defined in claim 24, wherein the sensor chamber includes a relativehumidity sensor and a temperature sensor.
 26. A powder transport systemas defined in claim 24, wherein the sensor chamber includes a relativehumidity sensor and two temperature sensors to enable cross checking oftemperature readings.
 27. A powder transport system as defined in claim24, wherein the sensor chamber has an internal volume that is comparableto an internal volume of the powder dispenser assembly.
 28. A powdertransport system as defined in claim 24, wherein the gas conditioningelement comprises an induction rod to introduce conditioned transportgas into the blower assembly.
 29. A powder dispenser assemblycomprising: an array block including an array of vertical ports andhorizontal channels intersecting respective rows of the vertical ports;and powder dispenser modules mounted in respective vertical ports of thearray block, each of the powder dispenser modules having a powder inletcommunicating with the channel in the array block, wherein powderdelivered to the channels in the array block is dispensed by each of thepowder dispenser modules.
 30. A powder dispenser assembly as defined inclaim 29, wherein each channel in the array block passes through thearray block.
 31. A powder dispenser assembly as defined in claim 29,wherein the powder inlets of the powder dispenser modules are alignedwith the channels in the array block so that powder delivered to thechannels in the array block passes through powder inlets to downstreampowder dispenser modules.
 32. A powder dispenser assembly as defined inclaim 29, wherein the channels in the array block have sufficientcapacity to store powder for the powder dispenser modules.
 33. A powderdispenser assembly as defined in claim 29, wherein the channels in thearray block are slot shaped.
 34. A powder dispenser assembly as definedin claim 29, wherein the channels in the array block and the powderinlets of the powder dispenser modules have cross sections ofsubstantially equal size and shape.
 35. A powder dispenser assembly asdefined in claim 29, wherein each of the powder dispenser modulesincludes a housing that defines the powder inlet, a powder outlet, and apowder delivery conduit connecting the powder inlet and the powderoutlet, and a feed mechanism to move powder through the conduit to thepowder outlet.
 36. A powder aerator comprising: a manifold blockdefining a powder inlet, powder output ports and a transport gas inlet;a pneumatic broom to deliver powder to the powder output ports; a dumpvalve to supply a quantity of powder from the powder inlet to thepneumatic broom; a bypass manifold coupled to the powder output ports;and a crossover valve to direct selected portions of a transport gasfrom the transport gas inlet to the pneumatic broom and to the bypassmanifold.
 37. A powder aerator as defined in claim 36, furthercomprising flow straighteners and a contoured flow element to assist inproviding a uniform flow of the transport gas through the powder outputports.
 38. A powder aerator as defined in claim 36, wherein the manifoldblock further defines riser tubes connecting the pneumatic broom to thepowder output ports.
 39. A powder aerator as defined in claim 36,wherein the pneumatic broom includes a hollow aerator tube havingdischarge nozzles thereon.
 40. A powder aerator as defined in claim 39,wherein the discharge nozzles are substantially tangential to theaerator tube.
 41. A powder aerator as defined in claim 39, wherein thedischarge nozzles have a helical arrangement on the aerator tube.
 42. Apowder aerator as defined in claim 39, wherein the pneumatic broomfurther comprises one or more dividers on the aerator tube, which defineannular chambers.
 43. A powder aerator as defined in claim 39, furthercomprising an aerator core positioned in the aerator tube to assist inequalizing flow of the transport gas through the discharge nozzles. 44.A powder aerator as defined in claim 39, wherein the pneumatic broomfurther includes a flow director coupled between the crossover valve andthe aerator tube, the flow director having vanes to block and break uppowder agglomerates.
 45. A blower assembly comprising: an impeller tomove a transport gas; an impeller motor to rotate the impeller; a blowerhousing enclosing the impeller and having a discharge port for thetransport gas; a manifold to receive the transport gas; and agas-particle separation device to accumulate agglomerates entrained inthe transport gas.
 46. A blower assembly as defined in claim 45, furthercomprising an induction rod to introduce conditioned transport gas intothe separator.
 47. A blower assembly as defined in claim 45, wherein theimpeller is configured to produce dynamic shock waves at the dischargeport.
 48. A blower assembly as defined in claim 45, wherein thegas-particle separation device comprises a cyclone separator disposedbetween the manifold and the impeller.
 49. A blower assembly as definedin claim 45, wherein the gas-particle separation device comprises a vaneseparator disposed between the manifold and the impeller.
 50. A powdertransport system comprising: an array block, including an array ofvertical ports and horizontal channels intersecting respective rows ofvertical ports; powder dispenser modules mounted in respective verticalports of the array block, each of the powder dispenser modules having apowder inlet communicating with the channel in the array block, whereinpowder delivered to the channels in the array block is dispensed by theeach of the powder dispenser modules; a blower assembly to move atransport gas; a powder aerator to deliver powder entrained in thetransport gas to the horizontal channels in the array block; a hopperassembly to supply powder to the powder aerator; and a suction manifoldto return the transport gas to the blower assembly.